Drug Safety

, Volume 29, Issue 9, pp 735–768 | Cite as

Therapeutic Drug Monitoring and Pharmacogenetic Tests as Tools in Pharmacovigilance

  • Eveline Jaquenoud Sirot
  • Jan Willem van der Velden
  • Katharina Rentsch
  • Chin B. Eap
  • Pierre Baumann
Leading Article


Therapeutic drug monitoring (TDM) and pharmacogenetic tests play a major role in minimising adverse drug reactions and enhancing optimal therapeutic response. The response to medication varies greatly between individuals, according to genetic constitution, age, sex, co-morbidities, environmental factors including diet and lifestyle (e.g. smoking and alcohol intake), and drug-related factors such as pharmacokinetic or pharmacodynamic drug-drug interactions. Most adverse drug reactions are type A reactions, i.e. plasma-level dependent, and represent one of the major causes of hospitalisation, in some cases leading to death. However, they may be avoidable to some extent if pharmacokinetic and pharmacogenetic factors are taken into consideration.

This article provides a review of the literature and describes how to apply and interpret TDM and certain pharmacogenetic tests and is illustrated by case reports. An algorithm on the use of TDM and pharmacogenetic tests to help characterise adverse drug reactions is also presented. Although, in the scientific community, differences in drug response are increasingly recognised, there is an urgent need to translate this knowledge into clinical recommendations. Databases on drug-drug interactions and the impact of pharmacogenetic polymorphisms and adverse drug reaction information systems will be helpful to guide clinicians in individualised treatment choices.



No sources of funding were used in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.


  1. 1.
    Alexanderson B, Evans DA, Sjoqvist F. Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy. BMJ 1969; 4(686): 764–8PubMedCrossRefGoogle Scholar
  2. 2.
    Alexanderson B. Prediction of steady-state plasma levels of nortriptyline from single oral dose kinetics: a study in twins. Eur J Clin Pharmacol 1973; 6(1): 44–53PubMedCrossRefGoogle Scholar
  3. 3.
    Mahgoub A, Idle JR, Dring LG, et al. Polymorphic hydroxylation of debrisoquine in man. Lancet 1977; II(8038): 584–6CrossRefGoogle Scholar
  4. 4.
    Bertilsson L, Mellstrom B, Sjoqvist F, et al. Slow hydroxylation of nortriptyline and concomitant poor debrisoquine hydroxylation: clinical implications. Lancet 1981; I(8219): 560–1CrossRefGoogle Scholar
  5. 5.
    Ingelman-Sundberg M. Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J Intern Med 2001; 250(3): 186–200PubMedCrossRefGoogle Scholar
  6. 6.
    Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet 2000; 356(9242): 1667–71PubMedCrossRefGoogle Scholar
  7. 7.
    Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med 2005; 352(21): 2211–21PubMedCrossRefGoogle Scholar
  8. 8.
    Classen DC, Pestotnik SL, Evans RS, et al. Computerized surveillance of adverse drug events in hospital patients. JAMA 1991; 266(20): 2847–51PubMedCrossRefGoogle Scholar
  9. 9.
    von Euler M, Eliasson E, Ohlen G, et al. Adverse drug reactions causing hospitalization can be monitored from computerized medical records and thereby indicate the quality of drug utilization. Pharmacoepidemiol Drug Saf 2006; 15(3): 179–84CrossRefGoogle Scholar
  10. 10.
    Green CF, Mottram DR, Rowe PH, et al. Adverse drug reactions as a cause of admission to an acute medical assessment unit: a pilot study. J Clin Pharm Ther 2000; 25(5): 355–61PubMedCrossRefGoogle Scholar
  11. 11.
    Lapeyre-Mestre M, Gary J, Machelard-Roumagnac M, et al. Incidence and cost of adverse drug reactions in a French cancer institute. Eur J Clin Pharmacol 1997; 53(1): 19–22PubMedCrossRefGoogle Scholar
  12. 12.
    Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279(15): 1200–5PubMedCrossRefGoogle Scholar
  13. 13.
    Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329(7456): 15–9PubMedCrossRefGoogle Scholar
  14. 14.
    Dormann H, Criegee-Rieck M, Neubert A, et al. Lack of awareness of community-acquired adverse drug reactions upon hospital admission: dimensions and consequences of a dilemma. Drug Saf 2003; 26(5): 353–62PubMedCrossRefGoogle Scholar
  15. 15.
    Queneau P, Bannwarth B, Carpentier F, et al. Adverse drug effects observed at French admissions departments and emergency services (Prospective study of the National Educational Association for Teaching Therapeutics and proposals for preventive measures [in French]. Bull Acad Natl Med 2003; 187(4): 647–66PubMedGoogle Scholar
  16. 16.
    Johnson JA, Bootman JL. Drug-related morbidity and mortality: a cost-of-illness model. Arch Intern Med 1995; 155(18): 1949–56PubMedCrossRefGoogle Scholar
  17. 17.
    Lepori V, Perren A, Marone C. Adverse internal medicine drug effects at hospital admission [in German]. Schweiz Med Wochenschr 1999; 129(24): 915–22PubMedGoogle Scholar
  18. 18.
    Schneeweiss S, Hasford J, Gottler M, et al. Admissions caused by adverse drug events to internal medicine and emergency departments in hospitals: a longitudinal population-based study. Eur J Clin Pharmacol 2002; 58(4): 285–91PubMedCrossRefGoogle Scholar
  19. 19.
    McDonnell PJ, Jacobs MR. Hospital admissions resulting from preventable adverse drug reactions. Ann Pharmacother 2002; 36(9): 1331–6PubMedCrossRefGoogle Scholar
  20. 20.
    Classen DC, Pestotnik SL, Evans RS, et al. Adverse drug events in hospitalized patients: excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277(4): 301–6PubMedCrossRefGoogle Scholar
  21. 21.
    Bates DW, Spell N, Cullen DJ, et al. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA 1997; 277(4): 307–11PubMedCrossRefGoogle Scholar
  22. 22.
    Ozdemir V, Shear NH, Kalow W. What will be the role of pharmacogenetics in evaluating drug safety and minimising adverse effects? Drug Saf 2001; 24(2): 75–85PubMedCrossRefGoogle Scholar
  23. 23.
    Phillips KA, Veenstra DL, Oren E, et al. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA 2001; 286(18): 2270–9PubMedCrossRefGoogle Scholar
  24. 24.
    Guidance for Industry Pharmacogenomic Data Submissions [online]. Available from URL: http://www.fda.gov/cder/guidance/6400fnl.htm [Accessed 2006 Aug 9]Google Scholar
  25. 25.
    Mancama D, Arranz MJ, Kerwin RW. Genetic predictors of therapeutic response to clozapine: current status of research. CNS Drugs 2002; 16(5): 317–24PubMedCrossRefGoogle Scholar
  26. 26.
    Van der Weide J, Steijns LS, van Weelden MJ. The effect of smoking and cytochrome P450 CYP1A2 genetic polymorphism on clozapine clearance and dose requirement. Pharmacogenetics 2003; 13(3): 169–72PubMedCrossRefGoogle Scholar
  27. 27.
    Eap CB, Bender S, Sirot EJ, et al. Nonresponse to clozapine and ultra-rapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. J Clin Psychopharmacol 2004; 24(2): 214–9PubMedCrossRefGoogle Scholar
  28. 28.
    Mancama D, Kerwin RW. Role of pharmacogenomics in individualising treatment with SSRIs. CNS Drugs 2003; 17(3): 143–51PubMedCrossRefGoogle Scholar
  29. 29.
    Lerer B, Macciardi F. Pharmacogenetics of antidepressant and mood-stabilizing drugs: a review of candidate-gene studies and future research directions. Int J Neuropsychopharmacol 2002; 5(3): 255–75PubMedCrossRefGoogle Scholar
  30. 30.
    Kirchheiner J, Brosen K, Dahl ML, et al. CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta Psychiatr Scand 2001; 104(3): 173–92PubMedCrossRefGoogle Scholar
  31. 31.
    Kirchheiner J, Nickchen K, Bauer M, et al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004; 9(5): 442–73PubMedCrossRefGoogle Scholar
  32. 32.
    Campbell TJ, Williams KM. Therapeutic drug monitoring: antiarrhythmic drugs. Br J Clin Pharmacol 2001; 52Suppl. 1: 21S–34SPubMedCrossRefGoogle Scholar
  33. 33.
    Girard T. Pharmakogenetik in der Anasthesie. Schweiz Med Forum 2004; 4: 1199–202Google Scholar
  34. 34.
    Lennard L. Therapeutic drug monitoring of antimetabolic cytotoxic drugs. Br J Clin Pharmacol 1999; 47(2): 131–43PubMedCrossRefGoogle Scholar
  35. 35.
    Lennard L. Therapeutic drug monitoring of cytotoxic drugs. Br J Clin Pharmacol 2001; 52Suppl. 1: 75S–87SPubMedCrossRefGoogle Scholar
  36. 36.
    Raetz Bravo AE, Tchambaz L, Kraehenbuehl-Melcher A, et al. Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy. Drug Saf 2005; 28(3): 263–75CrossRefGoogle Scholar
  37. 37.
    Starling RC, Hare JM, Hauptman P, et al. Therapeutic drug monitoring for everolismus in heart transplant recipients based on exposure-effect modeling. Am J Transplant 2004; 4(12): 2126–31PubMedCrossRefGoogle Scholar
  38. 38.
    Min DI, Perry PJ, Chen HY, et al. Cyclosporine trough concentrations in predicting allograft rejection and renal toxicity up to 12 months after renal transplantation. Pharmacotherapy 1998; 18(2): 282–7PubMedGoogle Scholar
  39. 39.
    Eadie MJ. The role of therapeutic drug monitoring in improving the cost effectiveness of anticonvulsant therapy. Clin Pharmacokinet 1995; 29(1): 29–35PubMedCrossRefGoogle Scholar
  40. 40.
    Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 356(9237): 1255–9PubMedCrossRefGoogle Scholar
  41. 41.
    Brown CS, Farmer RG, Soberman JE, et al. Pharmacokinetic factors in the adverse cardiovascular effects of antipsychotic drugs. Clin Pharmacokinet 2004; 43(1): 33–56PubMedCrossRefGoogle Scholar
  42. 42.
    Mjorndal T, Boman MD, Hagg S, et al. Adverse drug reactions as a cause for admissions to a department of internal medicine. Pharmacoepidemiol Drug Saf 2002; 11(1): 65–72PubMedCrossRefGoogle Scholar
  43. 43.
    Jaquenoud Sirot E, Eap CB, Baumann P. Bedeutung von TDM und Pharmakogenetik bei Untersuchungen über Arzneimittelsicherheit in der Psychiatrie. Psychopharmakotherapie 2003; 10(1): 5–10Google Scholar
  44. 44.
    Jaquenoud Sirot E, Zullino D. Guide to combination therapy in psychiatry with special emphasis on fluvoxamine. Hannover: Hannoversche Arzte-Verlags-Union, Hannover, 2000Google Scholar
  45. 45.
    Poolsup N, Li Wan PA, Knight TL. Pharmacogenetics and psychopharmacotherapy. J Clin Pharm Ther 2000; 25(3): 197–220PubMedCrossRefGoogle Scholar
  46. 46.
    Ng CH, Schweitzer I, Norman T, et al. The emerging role of pharmacogenetics: implications for clinical psychiatry. Aust N Z J Psychiatry 2004; 38(7): 483–9PubMedCrossRefGoogle Scholar
  47. 47.
    Coutts RT, Urichuk LJ. Polymorphic cytochromes P450 and drugs used in psychiatry. Cell Mol Neurobiol 1999; 19(3): 325–54PubMedCrossRefGoogle Scholar
  48. 48.
    Murray M. P450 enzymes: inhibition mechanisms, genetic regulation and effects of liver disease. Clin Pharmacokinet 1992; 23(2): 132–46PubMedCrossRefGoogle Scholar
  49. 49.
    Guengerich FP, Wu ZL, Bartleson CJ. Function of human cytochrome P450s: characterization of the orphans. Biochem Biophys Res Commun 2005; 338(1): 465–9PubMedCrossRefGoogle Scholar
  50. 50.
    Guengerich FP. Role of cytochrome P450 enzymes in drug-drug interactions. Adv Pharmacol 1997; 43: 7–35PubMedCrossRefGoogle Scholar
  51. 51.
    Rotger M, Colombo S, Furrer H, et al. Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet Genomics 2005; 15(1): 1–5PubMedCrossRefGoogle Scholar
  52. 52.
    Crettol S, Deglon JJ, Besson J, et al. Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment. Clin Pharmacol Ther 2005; 78(6): 593–604PubMedCrossRefGoogle Scholar
  53. 53.
    Hesse LM, Venkatakrishnan K, Court MH, et al. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos 2000; 28(10): 1176–83PubMedGoogle Scholar
  54. 54.
    Roh HK, Chung JY, Oh DY, et al. Plasma concentrations of haloperidol are related to CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients. Br J Clin Pharmacol 2001; 52(3): 265–71PubMedCrossRefGoogle Scholar
  55. 55.
    Baumann P, Zullino DF, Eap CB. Enantiomers’ potential in psychopharmacology: a critical analysis with special emphasis on the antidepressant escitalopram. Eur Neuropsychopharmacol 2002; 12(5): 433–44PubMedCrossRefGoogle Scholar
  56. 56.
    Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999; 286(5439): 487–91PubMedCrossRefGoogle Scholar
  57. 57.
    Vogel F. Moderne probleme der humangenetik. Ergebn Inn Med Kinderheilk 1959; 12: 52–125CrossRefGoogle Scholar
  58. 58.
    Pirmohamed M, Park BK. Genetic susceptibility to adverse drug reactions. Trends Pharmacol Sci 2001; 22 (6): 298–305CrossRefGoogle Scholar
  59. 59.
    Sutrop M. Pharmacogenetics: ethical issues. Bioethics 2004; 18 (4): iii–viiiCrossRefGoogle Scholar
  60. 60.
    Weber WW. Pharmacogenetics. 1st ed. New York: Oxford University Press, 1997Google Scholar
  61. 61.
    Bertilsson L, Aberg-Wistedt A, Gustafsson LL, et al. Extremely rapid hydroxylation of debrisoquine: a case report with implication for treatment with nortriptyline and other tricyclic antidepressants. Ther Drug Monit 1985; 7(4): 478–80PubMedCrossRefGoogle Scholar
  62. 62.
    Weinshilboum R. Inheritance and drug response. N Engl J Med 2003; 348(6): 529–37PubMedCrossRefGoogle Scholar
  63. 63.
    Meisel C, Gerloff T, Kirchheiner J, et al. Implications of pharmacogenetics for individualizing drug treatment and for study design. J Mol Med 2003; 81(3): 154–67PubMedGoogle Scholar
  64. 64.
    Lerer B. Pharmacogenetics of psychotropic drugs. New York: Cambridge University Press, 2002CrossRefGoogle Scholar
  65. 65.
    Lindpainter K. Pharmacogenetics and the future of medical practice. J Mol Med 2003; 81: 141–53Google Scholar
  66. 66.
    Evans WE, McLeod HL. Pharmacogenomics: drug disposition, drug targets, and side effects. N Engl J Med 2003; 348(6): 538–49PubMedCrossRefGoogle Scholar
  67. 67.
    Lundqvist E, Johansson I, Ingelman-Sundberg M. Genetic mechanisms for duplication and multiduplication of the human CYP2D6 gene and methods for detection of duplicated CYP2D6 genes. Gene 1999; 226(2): 327–38PubMedCrossRefGoogle Scholar
  68. 68.
    Dalen P, Dahl ML, Ruiz ML, et al. 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clin Pharmacol Ther 1998; 63(4): 444–52PubMedCrossRefGoogle Scholar
  69. 69.
    Lovlie R, Daly AK, Matre GE, et al. Polymorphisms in CYP2D6 duplication-negative individuals with the ultra-rapid metabolizer phenotype: a role for the CYP2D6*35 allele in ultra-rapid metabolism? Pharmacogenetics 2001; 11(1): 45–55PubMedCrossRefGoogle Scholar
  70. 70.
    Bergmann TK, Bathum L, Brosen K. Duplication of CYP2D6 predicts high clearance of desipramine but high clearance does not predict duplication of CYP2D6. Eur J Clin Pharmacol 2001; 57 (2): 123–7CrossRefGoogle Scholar
  71. 71.
    Xie HG, Kim RB, Wood AJ, et al. Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol 2001; 41: 815–50PubMedCrossRefGoogle Scholar
  72. 72.
    Pi EH, Simpson GM. Cross-cultural psychopharmacology: a current clinical perspective. Psychiatr Serv 2005; 56(1): 31–3PubMedCrossRefGoogle Scholar
  73. 73.
    Burroughs VJ, Maxey RW, Levy RA. Racial and ethnic differences in response to medicines: towards individualized pharmaceutical treatment. J Natl Med Assoc 2002; 94(10 Suppl.): 1–26PubMedGoogle Scholar
  74. 74.
    Ng CH, Chong SA, Lambert T, et al. An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels. Int Clin Psychopharmacol 2005; 20(3): 163–8PubMedCrossRefGoogle Scholar
  75. 75.
    Shimada T, Yamazaki H, Mimura M, et al. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994; 270(1): 414–23PubMedGoogle Scholar
  76. 76.
    Linnet K, Olesen OV. Metabolism of clozapine by cDNA-expressed human cytochrome P450 enzymes. Drug Metab Dispos 1997; 25(12): 1379–82PubMedGoogle Scholar
  77. 77.
    Goldstein JA, Ishizaki T, Chiba K, et al. Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics 1997; 7(1): 59–64PubMedCrossRefGoogle Scholar
  78. 78.
    Matsuda KT, Cho MC, Lin KM, et al. Clozapine dosage, serum levels, efficacy, and side-effect profiles: a comparison of Korean-American and Caucasian patients. Psychopharmacol Bull 1996; 32: 253–7PubMedGoogle Scholar
  79. 79.
    Nakajima M, Yokoi T, Mizutani M, et al. Genetic polymorphism in the 5′-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J Biochem (Tokyo) 1999; 125(4): 803–8CrossRefGoogle Scholar
  80. 80.
    Allorge D, Chevalier D, Lo-Guidice JM, et al. Identification of a novel splice-site mutation in the CYP1A2 gene. Br J Clin Pharmacol 2003; 56(3): 341–4PubMedCrossRefGoogle Scholar
  81. 81.
    Aklillu E, Carrillo JA, Makonnen E, et al. Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with singlenucleotide polymorphisms in intron 1. Mol Pharmacol 2003; 64(3): 659–69PubMedCrossRefGoogle Scholar
  82. 82.
    Sachse C, Brockmöller J, Bauer S, et al. Functional significance of a C → A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 1999; 47(4): 445–9PubMedCrossRefGoogle Scholar
  83. 83.
    Han XM, Ou-Yang DS, Lu PX, et al. Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734A polymorphisms of human CYP1A2. Pharmacogenetics 2001; 11(5): 429–35PubMedCrossRefGoogle Scholar
  84. 84.
    Aynacioglu AS, Brockmöller J, Bauer S, et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol 1999; 48(3): 409–15PubMedCrossRefGoogle Scholar
  85. 85.
    Garcia-Martin E, Martinez C, Ladero JM, et al. High frequency of mutations related to impaired CYP2C9 metabolism in a Caucasian population. Eur J Clin Pharmacol 2001; 57(1): 47–9PubMedCrossRefGoogle Scholar
  86. 86.
    Scordo MG, Caputi AP, D’Arrigo C, et al. Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population. Pharmacol Res 2004; 50(2): 195–200PubMedCrossRefGoogle Scholar
  87. 87.
    Wang SL, Huang J, Lai MD, et al. Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese. Pharmacogenetics 1995; 5(1): 37–42PubMedCrossRefGoogle Scholar
  88. 88.
    Kimura M, Ieiri I, Mamiya K, et al. Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population. Ther Drug Monit 1998; 20(3): 243–7PubMedCrossRefGoogle Scholar
  89. 89.
    Scordo MG, Aklillu E, Yasar U, et al. Genetic polymorphism of cytochrome P4502C9 in a Caucasian and a black African population. Br J Clin Pharmacol 2001; 52(4): 447–50PubMedCrossRefGoogle Scholar
  90. 90.
    Gaedigk A. Interethnic differences of drug-metabolizing enzymes. Int J Clin Pharmacol Ther 2000; 38(2): 61–8PubMedGoogle Scholar
  91. 91.
    Dandara C, Masimirembwa CM, Magimba A, et al. Genetic polymorphism of CYP2D6 and CYP2C19 in east- and southern African populations including psychiatric patients. Eur J Clin Pharmacol 2001; 57(1): 11–7PubMedCrossRefGoogle Scholar
  92. 92.
    Evans DA, Krahn P, Narayanan N. The mephenytoin (cytochrome P4502C19). and dextromethorphan (cytochrome P4502D6). polymorphisms in Saudi Arabians and Filipinos. Pharmacogenetics 1995; 5(2): 64–71PubMedCrossRefGoogle Scholar
  93. 93.
    Aynacioglu AS, Sachse C, Bozkurt A, et al. Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population. Clin Pharmacol Ther 1999; 66(2): 185–92PubMedGoogle Scholar
  94. 94.
    Roh HK, Dahl ML, Johansson I, et al. Debrisoquine and Smephenytoin hydroxylation phenotypes and genotypes in a Korean population. Pharmacogenetics 1996; 6(5): 441–7PubMedCrossRefGoogle Scholar
  95. 95.
    Roh HK, Dahl ML, Tybring G, et al. CYP2C19 genotype and phenotype determined by omeprazole in a Korean population. Pharmacogenetics 1996; 6(6): 547–51PubMedCrossRefGoogle Scholar
  96. 96.
    Itoh K, Inoue K, Yanagiwara S, et al. A rapid and simple detection of genetic defects responsible for the phenotypic polymorphism of cytochrome P4502C19. Biol Pharm Bull 1999; 22(1): 77–9PubMedCrossRefGoogle Scholar
  97. 97.
    Kimura M, Ieiri I, Mamiya K, et al. Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population. Ther Drug Monit 1998; 20(3): 243–7PubMedCrossRefGoogle Scholar
  98. 98.
    Sachse C, Brockmöller J, Bauer S, et al. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 1997; 60(2): 284–95PubMedGoogle Scholar
  99. 99.
    Dahl AA, Lowert A, Asserson S, et al. Hydroxylation polymorphism of debrisoquine hydroxylase (CYP2D6) in patients with schizophrenia in Norway and Denmark. Hum Psychopharmacol Clin Exp 1998; 13: 509–11CrossRefGoogle Scholar
  100. 100.
    Tefre T, Daly AK, Armstrong M, et al. Genotyping of the CYP2D6 gene in Norwegian lung cancer patients and controls. Pharmacogenetics 1994; 4(2): 47–57PubMedCrossRefGoogle Scholar
  101. 101.
    Madsen H, Nielsen KK, Brosen K. Imipramine metabolism in relation to the sparteine and mephenytoin oxidation polymorphisms: a population study. Br J Clin Pharmacol 1995; 39(4): 433–9PubMedCrossRefGoogle Scholar
  102. 102.
    Agundez JA, Ledesma MC, Ladero JM, et al. Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population. Clin Pharmacol Ther 1995; 57(3): 265–9PubMedCrossRefGoogle Scholar
  103. 103.
    McLellan RA, Oscarson M, Seidegard J, et al. Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics 1997; 7(3): 187–91PubMedCrossRefGoogle Scholar
  104. 104.
    Ji L, Pan S, Wu J, et al. Genetic polymorphisms of CYP2D6 in Chinese mainland. Chin Med J (Engl) 2002; 115(12): 1780–4Google Scholar
  105. 105.
    Bradford LD, Gaedigk A, Leeder JS. High frequency of CYP2D6 poor and “intermediate” metabolizers in black populations: a review and preliminary data. Psychopharmacol Bull 1998; 34(4): 797–804PubMedGoogle Scholar
  106. 106.
    Bradford LD, Kirlin WG. Polymorphism of CYP2D6 in Black populations: implications for psychopharmacology. Int J Neuropsychopharmcol 1998; 1(2): 173–85CrossRefGoogle Scholar
  107. 107.
    Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 2002; 3(2): 229–43PubMedCrossRefGoogle Scholar
  108. 108.
    Kuehl P, Zhang J, Lin Y, et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 2001; 27(4): 383–91PubMedCrossRefGoogle Scholar
  109. 109.
    Saeki M, Saito Y, Nakamura T, et al. Single nucleotide polymorphisms and haplotype frequencies of CYP3A5 in a Japanese population. Hum Mutat 2003; 21(6): 653PubMedCrossRefGoogle Scholar
  110. 110.
    Chou FC, Tzeng SJ, Huang JD. Genetic polymorphism of cytochrome P450 3A5 in Chinese. Drug Metab Dispos 2001; 29(9): 1205–9PubMedGoogle Scholar
  111. 111.
    Dai D, Tang J, Rose R, et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther 2001; 299(3): 825–31PubMedGoogle Scholar
  112. 112.
    Bertilsson L, Lou YQ, Du YL, et al. Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and Smephenytoin. Clin Pharmacol Ther 1992; 51(4): 388–97PubMedCrossRefGoogle Scholar
  113. 113.
    Fukuda T, Yamamoto I, Nishida Y, et al. Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers. Br J Clin Pharmacol 1999; 47(4): 450–3PubMedCrossRefGoogle Scholar
  114. 114.
    Bertilsson L, Dahl ML, Dalen P, et al. Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol 2002; 53(2): 111–22PubMedCrossRefGoogle Scholar
  115. 115.
    Bertilsson L, Dahl ML, Tybring G. Pharmacogenetics of antidepressants: clinical aspects. Acta Psychiatr Scand Suppl 1997; 391: 14–21PubMedCrossRefGoogle Scholar
  116. 116.
    Kirchheiner J, Bertilsson L, Bruus H, et al. Individualized medicine: implementation of pharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders. Pharmacopsychiatry 2003; 36Suppl. 3: S235–43PubMedGoogle Scholar
  117. 117.
    Kirchheiner J, Fuhr U, Brockmöller J. Pharmacogenetics-based therapeutic recommendations: ready for clinical practice? Nat Rev Drug Discov 2005; 4(8): 639–47PubMedCrossRefGoogle Scholar
  118. 118.
    Lessard E, Yessine MA, Hamelin BA, et al. Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans. Pharmacogenetics 1999; 9(4): 435–43PubMedGoogle Scholar
  119. 119.
    Gasche Y, Daali Y, Fathi M, et al. Codeine intoxication associated with ultra-rapid CYP2D6 metabolism. N Engl J Med 2004; 351(27): 2827–31PubMedCrossRefGoogle Scholar
  120. 120.
    Dalen P, Frengell C, Dahl ML, et al. Quick onset of severe abdominal pain after codeine in an ultra-rapid metabolizer of debrisoquine. Ther Drug Monit 1997; 19(5): 543–4PubMedCrossRefGoogle Scholar
  121. 121.
    Baumann P, Hiemke C, Ulrich S, et al. The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 2004; 37(6): 243–65PubMedCrossRefGoogle Scholar
  122. 122.
    Stephan PL, Jaquenoud Sirot E, Mueller B, et al. Adverse drug reactions following nonresponse in a depressed patient with CYP2D6 deficiency and low CYP 3A4/5 activity: a pharmacovigilance case report. Pharmacopsychiatry 2006; 39(4): 150–2PubMedCrossRefGoogle Scholar
  123. 123.
    Furuta T, Shirai N, Xiao F, et al. Effect of high-dose lansoprazole on intragastic pH in subjects who are homozygous extensive metabolizers of cytochrome P4502C19. Clin Pharmacol Ther 2001; 70(5): 484–92PubMedCrossRefGoogle Scholar
  124. 124.
    Furuta T, Ohashi K, Kosuge K, et al. CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans. Clin Pharmacol Ther 1999; 65(5): 552–61PubMedCrossRefGoogle Scholar
  125. 125.
    Furuta T, Takashima M, Shirai N, et al. Cure of refractory duodenal ulcer and infection caused by Helicobacter pylori by high doses of omeprazole and amoxicillin in a homozygous CYP2C19 extensive metabolizer patient. Clin Pharmacol Ther 2000; 67(6): 684–9PubMedCrossRefGoogle Scholar
  126. 126.
    Furuta T, Shirai N, Takashima M, et al. Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin. Clin Pharmacol Ther 2001; 69(3): 158–68PubMedCrossRefGoogle Scholar
  127. 127.
    Furuta T, Ohashi K, Kamata T, et al. Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer. Ann Intern Med 1998; 129(12): 1027–30PubMedGoogle Scholar
  128. 128.
    Higashi MK, Veenstra DL, Kondo LM, et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 2002; 287(13): 1690–8PubMedCrossRefGoogle Scholar
  129. 129.
    Scordo MG, Pengo V, Spina E, et al. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin Pharmacol Ther 2002; 72(6): 702–10PubMedCrossRefGoogle Scholar
  130. 130.
    Hillman MA, Wilke RA, Yale SH, et al. A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data. Clin Med Res 2005; 3(3): 137–45PubMedCrossRefGoogle Scholar
  131. 131.
    Ozdemir V, Kalow W, Posner P, et al. CYP1A2 activity as measured by a caffeine test predicts clozapine and active metabolite steady-state concentration in patients with schizophrenia. J Clin Psychopharmacol 2001; 21(4): 398–407PubMedCrossRefGoogle Scholar
  132. 132.
    Eap CB, Buclin T, Hustert E, et al. Pharmacokinetics of midazolam in CYP3A4 and CYP3A5 genotyped subjects. Eur J Clin Pharmacol 2004; 60(4): 231–6PubMedGoogle Scholar
  133. 133.
    Shah RR. Pharmacogenetic aspects of drug-induced torsade de pointes: potential tool for improving clinical drug development and prescribing. Drug Saf 2004; 27(3): 145–72PubMedCrossRefGoogle Scholar
  134. 134.
    Brandolese R, Scordo MG, Spina E, et al. Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Clin Pharmacol Ther 2001; 70(4): 391–4PubMedGoogle Scholar
  135. 135.
    Kidd RS, Curry TB, Gallagher S, et al. Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics 2001; 11(9): 803–8PubMedCrossRefGoogle Scholar
  136. 136.
    Aithal GP, Day CP, Kesteven PJ, et al. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999; 353(9154): 717–9PubMedCrossRefGoogle Scholar
  137. 137.
    Kidd RS, Straughn AB, Meyer MC, et al. Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics 1999; 9(1): 71–80PubMedCrossRefGoogle Scholar
  138. 138.
    Miners JO, Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998; 45(6): 525–38PubMedCrossRefGoogle Scholar
  139. 139.
    Kapitany T, Meszaros K, Lenzinger E, et al. Genetic polymorphisms for drug metabolism (CYP2D6) and tardive dyskinesia in schizophrenia. Schizophr Res 1998; 32(2): 101–6PubMedCrossRefGoogle Scholar
  140. 140.
    Brosen K. Drug-metabolizing enzymes and therapeutic drug monitoring in psychiatry. Ther Drug Monit 1996; 18(4): 393–6PubMedCrossRefGoogle Scholar
  141. 141.
    Dahl ML, Sjoqvist F. Pharmacogenetic methods as a complement to therapeutic monitoring of antidepressants and neuroleptics. Ther Drug Monit 2000; 22(1): 114–7PubMedCrossRefGoogle Scholar
  142. 142.
    DeVane CL. Pharmacogenetics and drug metabolism of newer antidepressant agents. J Clin Psychiatry 1994; 55Suppl.: 38–45PubMedGoogle Scholar
  143. 143.
    Otani K, Aoshima T. Pharmacogenetics of classical and new antipsychotic drugs. Ther Drug Monit 2000; 22(1): 118–21PubMedCrossRefGoogle Scholar
  144. 144.
    Steimer W, Potter JM. Pharmacogenetic screening and therapeutic drugs. Clin Chim Acta 2002; 315(1-2): 137–55PubMedCrossRefGoogle Scholar
  145. 145.
    Wilke RA, Reif DM, Moore JH. Combinatorial pharmacogenetics. Nat Rev Drug Discov 2005; 4(11): 911–8PubMedCrossRefGoogle Scholar
  146. 146.
    Lange-Asschenfeldt C, Weigmann H, Hiemke C, et al. Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated symptomatology. J Clin Psychopharmacol 2002; 22(4): 440–1PubMedCrossRefGoogle Scholar
  147. 147.
    Mahlberg R, Kunz D, Sasse J, et al. Serotonin syndrome with tramadol and citalopram (letter). Am J Psychiatry 2004; 161(6): 1129PubMedCrossRefGoogle Scholar
  148. 148.
    Kesavan S, Sobala GM. Serotonin syndrome with fluoxetine plus tramadol. J R Soc Med 1999; 92(9): 474–5PubMedGoogle Scholar
  149. 149.
    Lin JH, Yamazaki M. Clinical relevance of P-glycoprotein in drug therapy. Drug Metab Rev 2003; 35(4): 417–54PubMedCrossRefGoogle Scholar
  150. 150.
    Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 2003; 42(1): 59–98PubMedCrossRefGoogle Scholar
  151. 151.
    Levy RH. Metabolic drug interactions. Philadelphia: Lippincott Williams & Wilkins, 2005Google Scholar
  152. 152.
    Lin JH, Lu AY. Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet 1998; 35(5): 361–90PubMedCrossRefGoogle Scholar
  153. 153.
    Olesen OV, Linnet K. Fluvoxamine-clozapine drug interaction: inhibition in vitro of five cytochrome P450 isoforms involved in clozapine metabolism. J Clin Psychopharmacol 2000; 20(1): 35–42PubMedCrossRefGoogle Scholar
  154. 154.
    Fang J, Coutts RT, McKenna KF, et al. Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine. Naunyn Schmiedebergs Arch Pharmacol 1998; 358(5): 592–9PubMedCrossRefGoogle Scholar
  155. 155.
    Eiermann B, Engel G, Johansson I, et al. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 1997; 44: 439–46PubMedCrossRefGoogle Scholar
  156. 156.
    Wienkers LC, Heath TG. Predicting in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Discov 2005; 4(10): 825–33PubMedCrossRefGoogle Scholar
  157. 157.
    Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 1997; 32(3): 210–58PubMedCrossRefGoogle Scholar
  158. 158.
    Bonnabry P, Sievering J, Leemann T, et al. Quantitative drug interactions prediction system (Q-DIPS): a dynamic computerbased method to assist in the choice of clinically relevant in vivo studies. Clin Pharmacokinet 2001; 40(9): 631–40PubMedCrossRefGoogle Scholar
  159. 159.
    Lin JH, Lu AY. Interindividual variability in inhibition and induction of cytochrome P450 enzymes. Annu Rev Pharmacol Toxicol 2001; 41: 535–67PubMedCrossRefGoogle Scholar
  160. 160.
    Schmider J, Von Moltke LL, Shader RI, et al. Extrapolating in vitro data on drug metabolism to in vivo pharmacokinetics: evaluation of the pharmacokinetic interaction between amitriptyline and fluoxetine. Drug Metab Rev 1999; 31(2): 545–60PubMedCrossRefGoogle Scholar
  161. 161.
    Obach RS, Walsky RL, Venkatakrishnan K, et al. In vitro cytochrome P450 inhibition data and the prediction of drug-drug interactions: qualitative relationships, quantitative predictions, and the rank-order approach. Clin Pharmacol Ther 2005; 78(6): 582–92PubMedCrossRefGoogle Scholar
  162. 162.
    Obach RS, Walsky RL, Venkatakrishnan K, et al. The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactions. J Pharmacol Exp Ther 2006; 316(1): 336–48PubMedCrossRefGoogle Scholar
  163. 163.
    Lane R, Baldwin D. Selective serotonin reuptake inhibitor-induced serotonin syndrome: review. J Clin Psychopharmacol 1997; 17(3): 208–21PubMedCrossRefGoogle Scholar
  164. 164.
    Morales N, Vermette H. Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine. Psychosomatics 2005; 46(3): 274–5PubMedCrossRefGoogle Scholar
  165. 165.
    Bhatara VS, Magnus RD, Paul KL, et al. Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms. Ann Pharmacother 1998; 32(4): 432–6PubMedCrossRefGoogle Scholar
  166. 166.
    Coplan JD, Gorman JM. Detectable levels of fluoxetine metabolites after discontinuation: an unexpected serotonin syndrome. Am J Psychiatry 1993; 150(5): 837PubMedGoogle Scholar
  167. 167.
    Ciraulo DA, Shader RI, Greenblatt DJ, et al. Basic concepts. In: Ciraulo DA, Shader RI, Greenblatt DJ, et al., editors. Drug interactions in psychiatry. Maryland, USA: Williams & Wilkins, 1995: 1–28Google Scholar
  168. 168.
    Saito M, Yasui-Furukori N, Nakagami T, et al. Dose-dependent interaction of paroxetine with risperidone in schizophrenic patients. J Clin Psychopharmacol 2005; 25(6): 527–32PubMedCrossRefGoogle Scholar
  169. 169.
    Paus E, Jonzier-Perey M, Cochard N, et al. Chirality in the new generation of antidepressants: stereoselective analysis of the enantiomers of mirtazapine, N-demethylmirtazapine, and 8-hydroxymirtazapine by LC-MS. Ther Drug Monit 2004; 26(4): 366–74PubMedCrossRefGoogle Scholar
  170. 170.
    Bondolfi G, Chautems C, Rochat B, et al. Non-response to citalopram in depressive patients: pharmacokinetic and clinical consequences of a fluvoxamine augmentation. Psychopharmacology (Berl) 1996; 128 (4): 421–5CrossRefGoogle Scholar
  171. 171.
    Bondolfi G, Lissner C, Kosel M, et al. Fluoxetine augmentation in citalopram non-responders: pharmacokinetic and clinical consequences. Int J Neuropsychopharmacol 2000; 3(1): 55–60PubMedCrossRefGoogle Scholar
  172. 172.
    Eap CB, Bertel-Laubscher R, Zullino D, et al. Marked increase of venlafaxine enantiomer concentrations as a consequence of metabolic interactions: a case report. Pharmacopsychiatry 2000; 33(3): 112–5PubMedCrossRefGoogle Scholar
  173. 173.
    Steinacher L, Vandel P, Zullino DF, et al. Carbamazepine augmentation in depressive patients non-responding to citalopram: a pharmacokinetic and clinical pilot study. Eur Neuropsychopharmacol 2002; 12(3): 255–60PubMedCrossRefGoogle Scholar
  174. 174.
    Gibaldi M. Stereoselective and isozyme-selective drug interactions. Chirality 1993; 5(6): 407–13PubMedCrossRefGoogle Scholar
  175. 175.
    Gidal BE, Sorkness CA, McGill KA, et al. Evaluation of a potential enantioselective interaction between ticlopidine and warfarin in chronically anticoagulated patients. Ther Drug Monit 1995; 17(1): 33–8PubMedCrossRefGoogle Scholar
  176. 176.
    Ciusani E, Zullino DF, Eap CB, et al. Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects. J Psychopharmacol 2004; 18(4): 559–66PubMedCrossRefGoogle Scholar
  177. 177.
    Zhou Q, Chan E. Effect of omeprazole on the anticoagulant activity and the pharmacokinetics of warfarin enantiomers in rats. Eur J Pharm Sci 2003; 20(4-5): 439–49PubMedCrossRefGoogle Scholar
  178. 178.
    Andersson T, Hassan-Alin M, Hasselgren G, et al. Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole. Clin Pharmacokinet 2001; 40(7): 523–37PubMedCrossRefGoogle Scholar
  179. 179.
    Knezevic B, Ramseier F, Jaquenoud Sirot E. Clozapine-fluvoxamine combination therapy: how much fluvoxamine? Results from a case series. Eur Psychiatry 2006; 21: S225Google Scholar
  180. 180.
    Armstrong SC, Stephans JR. Blood clozapine levels elevated by fluvoxamine: potential for side effects and lower clozapine dosage. J Clin Psychiatry 1997; 58(11): 499PubMedCrossRefGoogle Scholar
  181. 181.
    Lu ML, Lane HY, Lin SK, et al. Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances. J Clin Psychiatry 2004; 65(6): 766–71PubMedCrossRefGoogle Scholar
  182. 182.
    Silver H, Kaplan A, Jahjah N. Fluvoxamine augmentation for clozapine-resistant schizophrenia. Am J Psychiatry 1995; 152(7): 1098PubMedGoogle Scholar
  183. 183.
    Szegedi A, Anghelescu I, Wiesner J, et al. Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial. Pharmacopsychiatry 1999; 32(4): 148–53PubMedCrossRefGoogle Scholar
  184. 184.
    Wetzel H, Anghelescu I, Szegedi A, et al. Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol 1998; 18(1): 2–9PubMedCrossRefGoogle Scholar
  185. 185.
    Silver H. Fluvoxamine as an adjunctive agent in schizophrenia. CNS Drug Rev 2001; 7(3): 283–304PubMedCrossRefGoogle Scholar
  186. 186.
    Fabrazzo M, La Pia S, Monteleone P, et al. Fluvoxamine increases plasma and urinary levels of clozapine and its major metabolites in a time- and dose-dependent manner. J Clin Psychopharmacol 2000; 20(6): 708–10PubMedCrossRefGoogle Scholar
  187. 187.
    Christensen M, Tybring G, Mihara K, et al. Low daily 10mg and 20mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19). Clin Pharmacol Ther 2002; 71(3): 141–52PubMedCrossRefGoogle Scholar
  188. 188.
    Clarke SM, Mulcahy FM, Tjia J, et al. The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz. Br J Clin Pharmacol 2001; 51(3): 213–7PubMedCrossRefGoogle Scholar
  189. 189.
    Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet 2002; 41(14): 1153–1193PubMedCrossRefGoogle Scholar
  190. 190.
    Marzolini C, Troillet N, Telenti A, et al. Efavirenz decreases methadone blood concentrations. AIDS 2000; 14(9): 1291–2PubMedCrossRefGoogle Scholar
  191. 191.
    Clarke SM, Mulcahy FM, Tjia J, et al. Pharmacokinetic interactions of nevirapine and methadone and guidelines for use of nevirapine to treat injection drug users. Clin Infect Dis 2001; 33(9): 1595–7PubMedCrossRefGoogle Scholar
  192. 192.
    Faber MS, Fuhr U. Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Clin Pharmacol Ther 2004; 76(2): 178–84PubMedCrossRefGoogle Scholar
  193. 193.
    Cozza KL, Armstrong SC, Oesterheld JR. Concise guide to drug interaction principles for medical practice. 2nd ed. Arlington (VA): American Psychiatric Publishing, Inc., 2003Google Scholar
  194. 194.
    Yue QY, Tomson T, Sawe J. Carbamazepine and cigarette smoking induce differentially the metabolism of codeine in man. Pharmacogenetics 1994; 4(4): 193–8PubMedCrossRefGoogle Scholar
  195. 195.
    Bondolfi G, Morel F, Crettol S, et al. Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients. Ther Drug Monit 2005; 27(4): 539–43PubMedCrossRefGoogle Scholar
  196. 196.
    de Leon J. Atypical antipsychotic dosing: the effect of smoking and caffeine. Psychiatr Serv 2004; 55(5): 491–3PubMedCrossRefGoogle Scholar
  197. 197.
    Zullino DF, Delessert D, Eap CB, et al. Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine. Int Clin Psychopharmacol 2002; 17(3): 141–3PubMedCrossRefGoogle Scholar
  198. 198.
    Carrillo JA, Herraiz AG, Ramos SI, et al. Role of the smokinginduced cytochrome P450 (CYP)1A2 and polymorphic CYP2D6 in steady-state concentration of olanzapine. J Clin Psychopharmacol 2003; 23(2): 119–27PubMedCrossRefGoogle Scholar
  199. 199.
    Saito M, Hirata-Koizumi M, Matsumoto M, et al. Undesirable effects of citrus juice on the pharmacokinetics of drugs: focus on recent studies. Drug Saf 2005; 28(8): 677–94PubMedCrossRefGoogle Scholar
  200. 200.
    Bailey DG, Dresser GK. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs 2004; 4(5): 281–97PubMedCrossRefGoogle Scholar
  201. 201.
    Dahan A, Altman H. Food-drug interaction: grapefruit juice augments drug bioavailability: mechanism, extent and relevance. Eur J Clin Nutr 2004; 58(1): 1–9PubMedCrossRefGoogle Scholar
  202. 202.
    Martin J, Krum H. Cytochrome P450 drug interactions within the HMG-CoA reductase inhibitor class: are they clinically relevant? Drug Saf 2003; 26(1): 13–21PubMedCrossRefGoogle Scholar
  203. 203.
    Harris RZ, Jang GR, Tsunoda S. Dietary effects on drug metabolism and transport. Clin Pharmacokinet 2003; 42(13): 1071–88PubMedCrossRefGoogle Scholar
  204. 204.
    Mills E, Wu P, Johnston BC, et al. Natural health product-drug interactions: a systematic review of clinical trials. Ther Drug Monit 2005; 27(5): 549–57PubMedCrossRefGoogle Scholar
  205. 205.
    Carrillo JA, Herraiz AG, Ramos SI, et al. Effects of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients. J Clin Psychopharmacol 1998; 18(4): 311–6PubMedCrossRefGoogle Scholar
  206. 206.
    Raaska K, Raitasuo V, Laitila J, et al. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004; 94(1): 13–8PubMedCrossRefGoogle Scholar
  207. 207.
    Ferrari AR, Guerrini R, Gatti G, et al. Influence of dosage, age, and co-medication on plasma topiramate concentrations in children and adults with severe epilepsy and preliminary observations on correlations with clinical response. Ther Drug Monit 2003; 25(6): 700–8PubMedCrossRefGoogle Scholar
  208. 208.
    Gatti G, Ferrari AR, Guerrini R, et al. Plasma gabapentin concentrations in children with epilepsy: influence of age, relationship with dosage, and preliminary observations on correlation with clinical response. Ther Drug Monit 2003; 25(1): 54–60PubMedCrossRefGoogle Scholar
  209. 209.
    Pollock BG. The pharmacokinetic imperative in late-life depression. J Clin Psychopharmacol 2005; 25(4 Suppl. 1): S19–23PubMedCrossRefGoogle Scholar
  210. 210.
    Cotreau MM, Von Moltke LL, Greenblatt DJ. The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin Pharmacokinet 2005; 44(1): 33–60PubMedCrossRefGoogle Scholar
  211. 211.
    Byerly MJ, Weber MT, Brooks DL, et al. Antipsychotic medications and the elderly: effects on cognition and implications for use. Drugs Aging 2001; 18(1): 45–61PubMedCrossRefGoogle Scholar
  212. 212.
    Barbui C, Nose M, Bindman J, et al. Sex differences in the subjective tolerability of antipsychotic drugs. J Clin Psychopharmacol 2005; 25(6): 521–6PubMedCrossRefGoogle Scholar
  213. 213.
    Clark R. Sex differences in antiretroviral therapy-associated intolerance and adverse events. Drug Saf 2005; 28(12): 1075–83PubMedCrossRefGoogle Scholar
  214. 214.
    Seeman MV. Gender differences in the prescribing of antipsychotic drugs. Am J Psychiatry 2004; 161(8): 1324–33PubMedCrossRefGoogle Scholar
  215. 215.
    Rademaker M. Do women have more adverse drug reactions? Am J Clin Dermatol 2001; 2(6): 349–51PubMedCrossRefGoogle Scholar
  216. 216.
    Jaquenoud Sirot E, Eap CBBP. Follow-up study using TDM and pharmacogenetic testing as tools in pharmacovigilance [abstract]. Drug Saf 2004; 27(12): 937Google Scholar
  217. 217.
    Pollock BG. Gender differences in psychotropic drug metabolism. Psychopharmacol Bull 1997; 33(2): 235–41PubMedGoogle Scholar
  218. 218.
    Perry PJ, Bever KA, Arndt S, et al. Relationship between patient variables and plasma clozapine concentrations: a dosing nomogram. Biol Psychiatry 1998; 44(8): 733–8PubMedCrossRefGoogle Scholar
  219. 219.
    Lane HY, Chang YC, Chang WH, et al. Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry 1999; 60(1): 36–40PubMedCrossRefGoogle Scholar
  220. 220.
    Weiss U, Marksteiner J, Kemmler G, et al. Effects of age and sex on olanzapine plasma concentrations. J Clin Psychopharmacol 2005; 25(6): 570–4PubMedCrossRefGoogle Scholar
  221. 221.
    Beierle I, Meibohm B, Derendorf H. Gender differences in pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther 1999; 37(11): 529–47PubMedGoogle Scholar
  222. 222.
    Meibohm B, Beierle I, Derendorf H. How important are gender differences in pharmacokinetics? Clin Pharmacokinet 2002; 41(5): 329–42PubMedCrossRefGoogle Scholar
  223. 223.
    Hagg S, Spigset O, Dahlqvist R. Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers. Br J Clin Pharmacol 2001; 51(2): 169–73PubMedCrossRefGoogle Scholar
  224. 224.
    Hutson WR, Roehrkasse RL, Wald A. Influence of gender and menopause on gastric emptying and motility. Gastroenterology 1989; 96(1): 11–7PubMedGoogle Scholar
  225. 225.
    Haack MJ, Bak ML, Beurskens R, et al. Toxic rise of clozapine plasma concentrations in relation to inflammation. Eur Neuropsychopharmacol 2003; 13(5): 381–5PubMedCrossRefGoogle Scholar
  226. 226.
    Raaska K, Raitasuo V, Arstila M, et al. Bacterial pneumonia can increase serum concentration of clozapine. Eur J Clin Pharmacol 2002; 58(5): 321–2PubMedCrossRefGoogle Scholar
  227. 227.
    Bleau AM, Maurel P, Pichette V, et al. Interleukin-1beta, interleukin- 6, tumour necrosis factor-alpha and interferon-gamma released by a viral infection and an aseptic inflammation reduce CYP1A1, 1A2 and 3A6 expression in rabbit hepatocytes. Eur J Pharmacol 2003; 473(2-3): 197–206PubMedCrossRefGoogle Scholar
  228. 228.
    Crawford JH, Yang S, Zhou M, et al. Down-regulation of hepatic CYP1A2 plays an important role in inflammatory responses in sepsis. Crit Care Med 2004; 32(2): 502–8PubMedCrossRefGoogle Scholar
  229. 229.
    Aitken AE, Richardson TA, Morgan ET. Regulation of drug metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol 2006; 46: 123–49PubMedCrossRefGoogle Scholar
  230. 230.
    Richardson TA, Morgan ET. Hepatic cytochrome P450 gene regulation during endotoxin-induced inflammation in nuclear receptor knockout mice. J Pharmacol Exp Ther 2005; 314(2): 703–9PubMedCrossRefGoogle Scholar
  231. 231.
    Wolkenstein P, Loriot MA, Aractingi S, et al. Prospective evaluation of detoxification pathways as markers of cutaneous adverse reactions to sulphonamides in AIDS. Pharmacogenetics 2000; 10(9): 821–8PubMedCrossRefGoogle Scholar
  232. 232.
    Meisel P. Arylamine N-acetyltransferases and drug response. Pharmacogenomics 2002; 3(3): 349–66PubMedCrossRefGoogle Scholar
  233. 233.
    Wormhoudt LW, Commandeur JN, Vermeulen NP. Genetic polymorphisms of human N-acetyltransferase, cytochrome P450, glutathione-S-transferase, and epoxide hydrolase enzymes: relevance to xenobiotic metabolism and toxicity. Crit Rev Toxicol 1999; 29(1): 59–124PubMedCrossRefGoogle Scholar
  234. 234.
    Liston HL, Markowitz JS, DeVane CL. Drug glucuronidation in clinical psychopharmacology. J Clin Psychopharmacol 2001; 21(5): 500–15PubMedCrossRefGoogle Scholar
  235. 235.
    Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000; 61: 154–66PubMedCrossRefGoogle Scholar
  236. 236.
    Dorne JLCM, Walton K, Renwick AG. Polymorphic CYP2C19 and N-acetylation: human variability in kinetics and pathway-related uncertainty factors. Food Chem Toxicol 2003; 41(2): 225–45PubMedCrossRefGoogle Scholar
  237. 237.
    de Leon J. Glucuronidation enzymes, genes and psychiatry. Int J Neuropsychopharmacol 2003; 6: 57–72PubMedCrossRefGoogle Scholar
  238. 238.
    Burchell B. Genetic variation of human UDP-glucuronosyltransferase: implications in disease and drug glucuronidation. Am J Pharmacogenomics 2003; 3(1): 37–52PubMedCrossRefGoogle Scholar
  239. 239.
    Miners JO, McKinnon RA, Mackenzie PI. Genetic polymorphisms of UDP-glucuronosyltransferases and their functional significance. Toxicology 2002; 181-2: 453–6CrossRefGoogle Scholar
  240. 240.
    Burchell B, Hume R. Molecular genetic basis of Gilbert’s syndrome. J Gastroenterol Hepatol 1999; 14(10): 960–6PubMedCrossRefGoogle Scholar
  241. 241.
    Premawardhena A, Fisher CA, Liu YT, et al. The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications. Blood Cells Mol Dis 2003; 31(1): 98–101PubMedCrossRefGoogle Scholar
  242. 242.
    Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A 1998; 95(14): 8170–4PubMedCrossRefGoogle Scholar
  243. 243.
    Iyer L, Ratain MJ. Pharmacogenetics and cancer chemotherapy. Eur J Cancer 1998; 34(10): 1493–9PubMedCrossRefGoogle Scholar
  244. 244.
    Iyer L, King CD, Whitington PF, et al. Genetic predisposition to the metabolism of irinotecan (CPT-11): role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J Clin Invest 1998; 101(4): 847–54PubMedCrossRefGoogle Scholar
  245. 245.
    Strolin BM, Ruty B, Baltes E. Induction of endogenous pathways by antiepileptics and clinical implications. Fundam Clin Pharmacol 2005; 19(5): 511–29CrossRefGoogle Scholar
  246. 246.
    Anderson GD, Yau MK, Gidal BE, et al. Bidirectional interaction of valproate and lamotrigine in healthy subjects. Clin Pharmacol Ther 1996; 60(2): 145–56PubMedCrossRefGoogle Scholar
  247. 247.
    Page RL, O’Neil MG, Yarbrough DR, et al. Fatal toxic epidermal necrolysis related to lamotrigine administration. Pharmacotherapy 1998; 18(2): 392–8PubMedGoogle Scholar
  248. 248.
    Johns LE, Houlston RS. N-acetyl transferase-2 and bladder cancer risk: a meta-analysis. Environ Mol Mutagen 2000; 36(3): 221–7PubMedCrossRefGoogle Scholar
  249. 249.
    Green J, Banks E, Berrington A, et al. N-acetyltransferase 2 and bladder cancer: an overview and consideration of the evidence for gene-environment interaction. Br J Cancer 2000; 83(3): 412–7PubMedCrossRefGoogle Scholar
  250. 250.
    Spielberg SP. N-acetyltransferases: pharmacogenetics and clinical consequences of polymorphic drug metabolism. J Pharmacokinet Biopharm 1996; 24(5): 509–19PubMedGoogle Scholar
  251. 251.
    Hughes HB, BiehI JP, Jones A, et al. Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. Am Rev Tuberc 1954; 70(2): 266–73PubMedGoogle Scholar
  252. 252.
    Lee W, Lockhart AC, Kim RB, et al. Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development. Oncologist 2005; 10(2): 104–11PubMedCrossRefGoogle Scholar
  253. 253.
    Al Hadithy AF, de Boer NK, Derijks LJ, et al. Thiopurines in inflammatory bowel disease: pharmacogenetics, therapeutic drug monitoring and clinical recommendations. Dig Liver Dis 2005; 37(4): 282–97PubMedCrossRefGoogle Scholar
  254. 254.
    Yates CR, Krynetski EY, Loennechen T, et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 1997; 126(8): 608–14PubMedGoogle Scholar
  255. 255.
    Collie-Duguid ES, Pritchard SC, Powrie RH, et al. The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics 1999; 9(1): 37–42PubMedCrossRefGoogle Scholar
  256. 256.
    McLeod HL, Krynetski EY, Relling MV, et al. Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia 2000; 14(4): 567–72PubMedCrossRefGoogle Scholar
  257. 257.
    Schutz E, Gummert J, Mohr F, et al. Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet 1993; 341(8842): 436PubMedCrossRefGoogle Scholar
  258. 258.
    Coulthard SA, Matheson EC, Hall AG, et al. The clinical impact of thiopurine methyltransferase polymorphisms on thiopurine treatment. Nucleosides Nucleotides Nucleic Acids 2004; 23 (8-9): 1385–91CrossRefGoogle Scholar
  259. 259.
    Evans WE. Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy. Ther Drug Monit 2004; 26(2): 186–91PubMedCrossRefGoogle Scholar
  260. 260.
    Krynetski E, Evans WE. Drug methylation in cancer therapy: lessons from the TPMT polymorphism. Oncogene 2003; 22(47): 7403–13PubMedCrossRefGoogle Scholar
  261. 261.
    Spector R. Drug transport in the mammalian central nervous system: multiple complex systems: a critical analysis and commentary. Pharmacology 2000; 60(2): 58–73PubMedCrossRefGoogle Scholar
  262. 262.
    Doherty MM, Charman WN. The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism? Clin Pharmacokinet 2002; 41(4): 235–53PubMedCrossRefGoogle Scholar
  263. 263.
    Uhr M, Steckler T, Yassouridis A, et al. Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology 2000; 22(4): 380–7PubMedCrossRefGoogle Scholar
  264. 264.
    Roberts RL, Joyce PR, Mulder RT, et al. A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression. Pharmacogenomics J 2002; 2(3): 191–6PubMedCrossRefGoogle Scholar
  265. 265.
    Sun J, He ZG, Cheng G, et al. Multidrug resistance P-glycoprotein: crucial significance in drug disposition and interaction. Med Sci Monit 2004; 10(1): RA5–14PubMedGoogle Scholar
  266. 266.
    DuBuske LM. The role of P-glycoprotein and organic anion-transporting polypeptides in drug interactions. Drug Saf 2005; 28(9): 789–801PubMedCrossRefGoogle Scholar
  267. 267.
    Brinkmann U, Eichelbaum M. Polymorphisms in the ABC drug transporter gene MDR1. Pharmacogenomics J 2001; 1(1): 59–64PubMedCrossRefGoogle Scholar
  268. 268.
    Brinkmann U, Roots I, Eichelbaum M. Pharmacogenetics of the human drug-transporter gene MDR1: impact of polymorphisms on pharmacotherapy. Drug Discov Today 2001; 6(16): 835–9PubMedCrossRefGoogle Scholar
  269. 269.
    Kerb R, Hoffmeyer S, Brinkmann U. ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2. Pharmacogenomics 2001; 2(1): 51–64PubMedCrossRefGoogle Scholar
  270. 270.
    Sakaeda T, Nakamura T, Okumura K. MDR1 genotype-related pharmacokinetics and pharmacodynamics. Biol Pharm Bull 2002; 25(11): 1391–400PubMedCrossRefGoogle Scholar
  271. 271.
    Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 2000; 97(7): 3473–8PubMedCrossRefGoogle Scholar
  272. 272.
    Sadeque AJ, Wandel C, He H, et al. Increased drug delivery to the brain by P-glycoprotein inhibition. Clin Pharmacol Ther 2000; 68(3): 231–7PubMedCrossRefGoogle Scholar
  273. 273.
    Perry PJ, Pfohl BM, Holstad SG. The relationship between antidepressant response and tricyclic antidepressant plasma concentrations: a retrospective analysis of the literature using logistic regression analysis. Clin Pharmacokinet 1987; 13(6): 381–92PubMedCrossRefGoogle Scholar
  274. 274.
    Perry PJ, Zeilmann C, Arndt S. Tricyclic antidepressant concentrations in plasma: an estimate of their sensitivity and specificity as a predictor of response. J Clin Psychopharmacol 1994; 14(4): 230–40PubMedCrossRefGoogle Scholar
  275. 275.
    Ulrich S, Neuhof S, Braun V, et al. Therapeutic window of serum haloperidol concentration in acute schizophrenia and schizoaffective disorder. Pharmacopsychiatry 1998; 31(5): 163–9PubMedCrossRefGoogle Scholar
  276. 276.
    Ulrich S, Lauter J. Comprehensive survey of the relationship between serum concentration and therapeutic effect of amitriptyline in depression. Clin Pharmacokinet 2002; 41(11): 853–76PubMedCrossRefGoogle Scholar
  277. 277.
    Ulrich S, Wurthmann C, Brosz M, et al. The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia. Clin Pharmacokinet 1998; 34(3): 227–63PubMedCrossRefGoogle Scholar
  278. 278.
    Gex-Fabry M, Balant-Gorgia AE, Balant LP. Clomipramine concentration as a predictor of delayed response: a naturalistic study. Eur J Clin Pharmacol 1999; 54(12): 895–902PubMedCrossRefGoogle Scholar
  279. 279.
    Eilers R. Therapeutic drug monitoring for the treatment of psychiatric disorders: clinical use and cost effectiveness. Clin Pharmacokinet 1995; 29(6): 442–50PubMedCrossRefGoogle Scholar
  280. 280.
    Balant-Gorgia AE, Gex-Fabry M, Balant LP. Clinical pharmacokinetics of clomipramine. Clin Pharmacokinet 1991; 20(6): 447–62PubMedCrossRefGoogle Scholar
  281. 281.
    Baldessarini RJ, Cohen BM, Teicher MH. Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses. Arch Gen Psychiatry 1988; 45(1): 79–91PubMedCrossRefGoogle Scholar
  282. 282.
    Rao ML, Hiemke C, Grasmader K, et al. [Olanzapine: pharmacology, pharmacokinetics and therapeutic drug monitoring]. Fortschr Neurol Psychiatr 2001; 69(11): 510–7PubMedCrossRefGoogle Scholar
  283. 283.
    Hiemke C, Dragicevic A, Grander G. Therapeutic monitoring of new antipsychotic drugs. Ther Drug Monit 2004; 26(2): 156–60PubMedCrossRefGoogle Scholar
  284. 284.
    Asberg M, Sjoqvist F. On the role of plasma level monitoring of tricyclic antidepressants in clinical practice. Commun Psychopharmacol 1978; 2(5): 381–91PubMedGoogle Scholar
  285. 285.
    de Oliveira IR, Dardennes RM, Amorim ES, et al. Is there a relationship between antipsychotic blood levels and their clinical efficacy? An analysis of studies design and methodology. Fundam Clin Pharmacol 1995; 9(5): 488–502PubMedCrossRefGoogle Scholar
  286. 286.
    Gram LF. Plasma level monitoring of tricyclic antidepressants: methodological and pharmacokinetic considerations. Commun Psychopharmacol 1978; 2(5): 373–80PubMedGoogle Scholar
  287. 287.
    Preskorn SH, Burke MJ, Fast GA. Therapeutic drug monitoring: principles and practice. Psychiatr Clin North Am 1993; 16(3): 611–45PubMedGoogle Scholar
  288. 288.
    Van Putten T, Marder SR. Variable dose studies provide misleading therapeutic windows. J Clin Psychopharmacol 1986; 6(4): 249–50PubMedGoogle Scholar
  289. 289.
    Task Force on the Use of Laboratory Tests in Psychiatry. Tricyclic antidepressants: blood level measurements and clinical outcome: an APA Task Force report. Am J Psychiatry 1985; 142 (2): 155–62Google Scholar
  290. 290.
    Nyberg S, Nordstrom AL, Halldin C, et al. Positron emission tomography studies on D2 dopamine receptor occupancy and plasma antipsychotic drug levels in man. Int Clin Psychopharmacol 1995; 10Suppl. 3: 81–5PubMedGoogle Scholar
  291. 291.
    Sedvall G, Farde L, Hall H, et al. Utilization of radioligands in schizophrenia research. Clin Neurosci 1995; 3(2): 112–21PubMedGoogle Scholar
  292. 292.
    Rasmussen BB, Brosen K. Is therapeutic drug monitoring a case for optimizing clinical outcome and avoiding interactions of the selective serotonin reuptake inhibitors? Ther Drug Monit 2000; 22(2): 143–54PubMedCrossRefGoogle Scholar
  293. 293.
    Hammer WM, Brodiet BB. Application of isotope derivative technique to assay of secondary amines: estimation of desipramine by acetylation with H3-acetic anhydride. J Pharmacol Exp Ther 1967; 157(3): 503–8PubMedGoogle Scholar
  294. 294.
    Asberg M, Cronholm B, Sjoqvist F, et al. Relationship between plasma level and therapeutic effect of nortriptyline. BMJ 1971; 3(770): 331–4PubMedCrossRefGoogle Scholar
  295. 295.
    Mitchell PB. Therapeutic drug monitoring of psychotropic medications. Br J Clin Pharmacol 2001; 52: 45S–54SPubMedCrossRefGoogle Scholar
  296. 296.
    Bengtsson F. Therapeutic drug monitoring of psychotropic drugs. TDM “nouveau”. Ther Drug Monit 2004; 26(2): 145–51PubMedCrossRefGoogle Scholar
  297. 297.
    Vuille F, Amey M, Baumann P. Use of plasma level monitoring of antidepressants in clinical practice: towards an analysis of clinical utility. Pharmacopsychiatry 1991; 24(6): 190–5PubMedCrossRefGoogle Scholar
  298. 298.
    Gefvert O, Eriksson B, Persson P, et al. Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (risperdal consta) in patients with schizophrenia. Int J Neuropsychopharmacol 2005; 8(1): 27–36PubMedCrossRefGoogle Scholar
  299. 299.
    Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs 2002; 62(15): 2169–83PubMedCrossRefGoogle Scholar
  300. 300.
    Heller S, Hiemke C, Stroba G, et al. Assessment of storage and transport stability of new antidepressant and antipsychotic drugs for a nationwide TDM service. Ther Drug Monit 2004; 26(4): 459–61PubMedCrossRefGoogle Scholar
  301. 301.
    Morris RG, Holt DW, Armstrong VW, et al. Analytic aspects of cyclosporine monitoring, on behalf of the IFCC/IATDMCT Joint Working Group. Ther Drug Monit 2004; 26(2): 227–30PubMedCrossRefGoogle Scholar
  302. 302.
    Jusko WJ, Thomson AW, Fung J, et al. Consensus document: therapeutic monitoring of tacrolimus (FK-506). Ther Drug Monit 1995; 17(6): 606–14PubMedCrossRefGoogle Scholar
  303. 303.
    Shaw LM, Sollinger HW, Halloran P, et al. Mycophenolate mofetil: a report of the consensus panel. Ther Drug Monit 1995; 17(6): 690–9PubMedCrossRefGoogle Scholar
  304. 304.
    Yatscoff RW, Boeckx R, Holt DW, et al. Consensus guidelines for therapeutic drug monitoring of rapamycin: report of the consensus panel. Ther Drug Monit 1995; 17(6): 676–80PubMedCrossRefGoogle Scholar
  305. 305.
    Kappelhoff BS, Crommentuyn KM, de Maat MM, et al. Practical guidelines to interpret plasma concentrations of antiretroviral drugs. Clin Pharmacokinet 2004; 43(13): 845–53PubMedCrossRefGoogle Scholar
  306. 306.
    Acosta EP, Gerber JG. Position paper on therapeutic drug monitoring of antiretroviral agents. AIDS Res Hum Retroviruses 2002; 18(12): 825–34PubMedCrossRefGoogle Scholar
  307. 307.
    Peloquin CA. Tuberculosis drug serum levels. Clin Infect Dis 2001; 33(4): 584–5PubMedCrossRefGoogle Scholar
  308. 308.
    Regenthal R, Krueger M, Koeppel C, et al. Drug levels: therapeutic and toxic serum/plasma concentrations of common drugs. J Clin Monit Comput 1999; 15(7-8): 529–44PubMedCrossRefGoogle Scholar
  309. 309.
    Schulz M, Schmoldt A. Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie 2003; 58(7): 447–74PubMedGoogle Scholar
  310. 310.
    Ensom MH, Chang TK, Patel P. Pharmacogenetics: the therapeutic drug monitoring of the future? Clin Pharmacokinet 2001; 40(11): 783–802PubMedCrossRefGoogle Scholar
  311. 311.
    Chainuvati S, Nafziger AN, Leeder JS, et al. Combined phenotypic assessment of cytochrome p450 1A2, 2C9, 2C19, 2D6, and 3A, N-acetyltransferase-2, and xanthine oxidase activities with the “Cooperstown 5+1 cocktail”. Clin Pharmacol Ther 2003; 74(5): 437–47PubMedCrossRefGoogle Scholar
  312. 312.
    Jerdi MC, Daali Y, Oestreicher MK, et al. A simplified analytical method for a phenotyping cocktail of major CYP450 biotransformation routes. J Pharm Biomed Anal 2004; 35(5): 1203–12PubMedCrossRefGoogle Scholar
  313. 313.
    Streetman DS, Bleakley JF, Kim JS, et al. Combined phenotypic assessment of CYP1A2, CYP2C19, CYP2D6, CYP3A, Nacetyltransferase-2, and xanthine oxidase with the “Cooperstown cocktail”. Clin Pharmacol Ther 2000; 68(4): 375–83PubMedCrossRefGoogle Scholar
  314. 314.
    Dahl ML. Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? Clin Pharmacokinet 2002; 41(7): 453–70PubMedCrossRefGoogle Scholar
  315. 315.
    Schubert L. Ethical implications of pharmacogenetics - do slippery slope arguments matter? Bioethics 2004; 18(4): 361–78PubMedCrossRefGoogle Scholar
  316. 316.
    Netzer C, Biller-Andorno N. Pharmacogenetic testing, informed consent and the problem of secondary information. Bioethics 2004; 18(4): 344–60PubMedCrossRefGoogle Scholar
  317. 317.
    Smart A, Martin P, Parker M. Tailored medicine: whom will it fit? The ethics of patient and disease stratification. Bioethics 2004; 18(4): 322–42PubMedCrossRefGoogle Scholar
  318. 318.
    van Delden J, Bolt I, Kalis A, et al. Tailor-made pharmacotherapy: future developments and ethical challenges in the field of pharmacogenomics. Bioethics 2004; 18(4): 303–21PubMedCrossRefGoogle Scholar
  319. 319.
    Paul NW, Roses AD. Pharmacogenetics and pharmacogenomics: recent developments, their clinical relevance and some ethical, social, and legal implications. J Mol Med 2003; 81(3): 135–40Google Scholar
  320. 320.
    de Leon J, Barnhill J, Rogers T, et al. Pilot study of the cytochrome P450-2D6 genotype in a psychiatric state hospital. Am J Psychiatry 1998; 155(9): 1278–80PubMedGoogle Scholar
  321. 321.
    Chou WH, Yan FX, de Leon J, et al. Extension of a pilot study: impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness. J Clin Psychopharmacol 2000; 20(2): 246–51PubMedCrossRefGoogle Scholar
  322. 322.
    Rau T, Wohlleben G, Wuttke H, et al. CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study. Clin Pharmacol Ther 2004; 75(5): 386–93PubMedCrossRefGoogle Scholar
  323. 323.
    Tamminga WJ, Wemer J, Oosterhuis B, et al. Polymorphic drug metabolism (CYP2D6) and utilisation of psychotropic drugs in hospitalised psychiatric patients: a retrospective study. Eur J Clin Pharmacol 2003; 59(1): 57–64PubMedGoogle Scholar
  324. 324.
    Mulder H, Wilmink FW, Beumer TL, et al. The association between cytochrome P450 2D6 genotype and prescription patterns of antipsychotic and antidepressant drugs in hospitalized psychiatric patients: a retrospective follow-up study. J Clin Psychopharmacol 2005; 25(2): 188–91PubMedCrossRefGoogle Scholar
  325. 325.
    de Leon J, Susce MT, Pan RM, et al. The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J Clin Psychiatry 2005; 66(1): 15–27PubMedCrossRefGoogle Scholar
  326. 326.
    Brockmöller J, Kirchheiner J, Schmider J, et al. The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment. Clin Pharmacol Ther 2002; 72(4): 438–52PubMedCrossRefGoogle Scholar
  327. 327.
    de Leon J, Susce MT, Pan RM, et al. Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness. J Clin Psychopharmacol 2005; 25 (5): 448–56CrossRefGoogle Scholar
  328. 328.
    Armstrong M, Daly AK, Blennerhassett R, et al. Antipsychotic drug-induced movement disorders in schizophrenics in relation to CYP2D6 genotype. Br J Psychiatry 1997; 170: 23–6PubMedCrossRefGoogle Scholar
  329. 329.
    Reggiani K, Vandel P, Haffen E, et al. Effets indesirables extrapyramidaux des neuroleptiques et antidepresseurs: recherche de facteurs de risque: role du polymorphisme genetique du CYP2D6. L’Encephale 2000; 26(1): 62–7PubMedGoogle Scholar
  330. 330.
    Steimer W, Zopf K, von Amelunxen S, et al. Amitriptyline or not, that is the question: pharmacogenetic testing of CYP2D6 and CYP2C19 identifies patients with low or high risk for side effects in amitriptyline therapy. Clin Chem 2005; 51(2): 376–85PubMedCrossRefGoogle Scholar
  331. 331.
    Grasmader K, Verwohlt PL, Rietschel M, et al. Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. Eur J Clin Pharmacol 2004; 60(5): 329–36PubMedCrossRefGoogle Scholar
  332. 332.
    Rau T, Heide R, Bergmann K, et al. Effect of the CYP2D6 genotype on metoprolol metabolism persists during long-term treatment. Pharmacogenetics 2002; 12(6): 465–72PubMedCrossRefGoogle Scholar
  333. 333.
    Wuttke H, Rau T, Heide R, et al. Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects. Clin Pharmacol Ther 2002; 72(4): 429–37PubMedCrossRefGoogle Scholar
  334. 334.
    Basile VS, Ozdemir V, Masellis M, et al. A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia. Mol Psychiatry 2000; 5(4): 410–7PubMedCrossRefGoogle Scholar
  335. 335.
    Tiwari AK, Deshpande SN, Rao AR, et al. Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism. Pharmacogenomics J 2005; 5(1): 60–9PubMedCrossRefGoogle Scholar
  336. 336.
    Lerer B, Segman RH, Fangerau H, et al. Pharmacogenetics of tardive dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism. Neuropsychopharmacology 2002; 27(1): 105–19PubMedCrossRefGoogle Scholar
  337. 337.
    Ozdemir V, Basile VS, Masellis M, et al. Pharmacogenetic assessment of antipsychotic-induced movement disorders: contribution of the dopamine D3 receptor and cytochrome P450 1A2 genes. J Biochem Biophys Methods 2001; 47(1-2): 151–7PubMedCrossRefGoogle Scholar
  338. 338.
    Taube J, Halsall D, Baglin T. Influence of cytochrome P450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 2000; 96(5): 1816–9PubMedGoogle Scholar
  339. 339.
    Wilke RA, Carrillo MW, Ritchie MD. Pacific symposium on biocomputing: computational approaches for pharmacogenomics. Pharmacogenomics 2005; 6(2): 111–3PubMedCrossRefGoogle Scholar
  340. 340.
    Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 2005; 5(1): 6–13PubMedCrossRefGoogle Scholar
  341. 341.
    Veenstra DL, Higashi MK, Phillips KA. Assessing the cost-effectiveness of pharmacogenomics. AAPS PharmSci 2000; 2(3): E29PubMedCrossRefGoogle Scholar
  342. 342.
    Simmons SA, Perry PJ, Rickert ED, et al. Cost-benefit analysis of prospective pharmacokinetic dosing of nortriptyline in depressed inpatients. J Affect Disord 1985; 8(1): 47–53PubMedCrossRefGoogle Scholar
  343. 343.
    Preskorn SH, Fast GA. Therapeutic drug monitoring for antidepressants: efficacy, safety, and cost effectiveness. J Clin Psychiatry 1991; 52Suppl.: 23–33PubMedGoogle Scholar
  344. 344.
    Lundmark J, Bengtsson F, Nordin C, et al. Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients. Acta Psychiatr Scand 2000; 101 (5): 354–9CrossRefGoogle Scholar
  345. 345.
    Muller MJ, Dragicevic A, Fric M, et al. Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions? Pharmacopsychiatry 2003; 36(3): 98–104PubMedCrossRefGoogle Scholar
  346. 346.
    Chen S, Chou WH, Blouin RA, et al. The cytochrome P450 2D6 (CYP2D6) enzyme polymorphism: screening costs and influence on clinical outcomes in psychiatry. Clin Pharmacol Ther 1996; 60(5): 522–34PubMedCrossRefGoogle Scholar
  347. 347.
    Frueh FW, Gurwitz D. From pharmacogenetics to personalized medicine: a vital need for educating health professionals and the community. Pharmacogenomics 2004; 5(5): 571–9PubMedCrossRefGoogle Scholar
  348. 348.
    Hug H, Bagatto D, Dannecker R, et al. ADRIS: the adverse drug reactions information scheme. Pharmacogenetics 2003; 13(12): 767–72PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Eveline Jaquenoud Sirot
    • 1
  • Jan Willem van der Velden
    • 2
    • 3
  • Katharina Rentsch
    • 4
  • Chin B. Eap
    • 5
  • Pierre Baumann
    • 5
  1. 1.Psychiatrische Dienste Aargau AG, MediQ, Klinik KönigsfeldenBruggSwitzerland
  2. 2.Global Safety and Pharmacovigilance, PharmaNet AGZumikonSwitzerland
  3. 3.Postgraduate Programme in Pharmaceutical MedicineUniversité Libre de BruxellesBrusselsBelgium
  4. 4.Institut für Klinische ChemieUniversitätsspital ZürichZurichSwitzerland
  5. 5.Unité de Biochimie et Psychopharmacologie, Department of Psychiatry, Center for Psychiatric NeurosciencePrilly-LausanneSwitzerland

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