Clinical Pharmacokinetics

, Volume 39, Issue 2, pp 127–153 | Cite as

Clinically Significant Pharmacokinetic Interactions Between Dietary Caffeine and Medications

  • Juan A. CarrilloEmail author
  • Julio Benitez
Review Article Drug Interactions


Caffeine from dietary sources (mainly coffee, tea and soft drinks) is the most frequently and widely consumed CNS stimulant in the world today. Because of its enormous popularity, the consumption of caffeine is generally thought to be safe and long term caffeine intake may be disregarded as a medical problem. However, it is clear that this compound has many of the features usually associated with a drug of abuse. Furthermore, physicians should be aware of the possible contribution of dietary caffeine to the presenting signs and symptoms of patients.

The toxic effects of caffeine are extensions of their pharmacological effects. The most serious caffeine-related CNS effects include seizures and delirium. Other symptoms affecting the cardiovascular system range from moderate increases in heart rate to more severe cardiac arrhythmia. Although tolerance develops to many of the pharmacological effects of caffeine, tolerance may be overwhelmed by the nonlinear accumulation of caffeine when its metabolism becomes saturated. This might occur with high levels of consumption or as the result of a pharmacokinetic interaction between caffeine and over-the-counter or prescription medications.

The polycyclic aromatic hydrocarbon-inducible cytochrome P450 (CYP) 1A2 participates in the metabolism of caffeine as well as of a number of clinically important drugs. A number of drugs, including certain selective serotonin reuptake inhibitors (particularly fluvoxamine), antiarrhythmics (mexiletine), antipsychotics (clozapine), psoralens, idrocilamide and phenylpropanolamine, bronchodilators (furafylline and theophylline) and quinolones (enoxacin), have been reported to be potent inhibitors of this isoenzyme. This has important clinical implications, since drugs that are metabolised by, or bind to, the same CYP enzyme have a high potential for pharmacokinetic interactions due to inhibition of drug metabolism. Thus, pharmacokinetic interactions at the CYP1A2 enzyme level may cause toxic effects during concomitant administration of caffeine and certain drugs used for cardiovascular, CNS (an excessive dietary intake of caffeine has also been observed in psychiatric patients), gastrointestinal, infectious, respiratory and skin disorders. Unless a lack of interaction has already been demonstrated for the potentially interacting drug, dietary caffeine intake should be considered when planning, or assessing response to, drug therapy.

Some of the reported interactions of caffeine, irrespective of clinical relevance, might inadvertently cause athletes to exceed the urinary caffeine concentration limit set by sports authorities at 12 mg/L. Finally, caffeine is a useful and reliable probe drug for the assessment of CYP1A2 activity, which is of considerable interest for metabolic studies in human populations.


Caffeine Theophylline Clozapine Fluvoxamine Pharmacokinetic Interaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The investigations carried out in our Department were partly supported by grants CICYT-SAF96-0006 from Comisión Interministerial de Ciencia y Tecnología, UE95-0043 and UE97-0001 from Secretaría de Estado de Universidades, Investigación y Desarrollo (Madrid, Spain), BMH4-CT96-0291 from European Union, and PRI96060023 and PRI97C120 from Junta de Extremadura (Mérida, Spain).


  1. 1.
    Garattini S. Caffeine, coffee, and health. New York: Raven Press Ltd, 1993.Google Scholar
  2. 2.
    Barone JJ, Grice HC. Seventh International Caffeine Workshop, Santorini, Greece 13–17 June 1993. Food Chem Toxicol 1994; 326(1): 65–77.Google Scholar
  3. 3.
    Benowitz NL. Clinical pharmacology of caffeine. Annu Rev Med 1990; 41: 277–88.PubMedCrossRefGoogle Scholar
  4. 4.
    Stavric B. Methylxanthines: toxicity to humans. 2. Caffeine. Food Chem Toxicol 1988; 26(7): 645–62.PubMedCrossRefGoogle Scholar
  5. 5.
    Massey LK. Caffeine and the elderly. Drugs Aging 1998; 13(1): 43–50.PubMedCrossRefGoogle Scholar
  6. 6.
    James JE. Caffeine and health. London: Academic Press Ltd, 1991.Google Scholar
  7. 7.
    Lelo A, Miners JO, Robson R, et al. Assessment of caffeine exposure: caffeine content of beverages, caffeine intake, and plasma concentrations of methylxanthines. Clin Pharmacol Ther 1986; 39(1): 54–9.PubMedCrossRefGoogle Scholar
  8. 8.
    D’Amicis A, Viani R. The consumption of coffee. In: Garattini S, editor. Caffeine, coffee, and health. New York: Raven Press Ltd, 1993: 1–16.Google Scholar
  9. 9.
    Barone JJ, Roberts HR. Caffeine consumption. Food Chem Toxicol 1996; 346(1): 119–29.Google Scholar
  10. 10.
    Serafin WE. Drugs used in the treatment of asthma. In: Hardman JG, Limbird LE, Molinoff PB, et al., editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw Hill, 1996: 659–82.Google Scholar
  11. 11.
    Sawynok J. Pharmacological rationale for the clinical use of caffeine. Drugs 1995; 49(1): 37–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Ellinwood EH, Lee TH. Central nervous system stimulants and anorectic agents. In: Dukes MNG, editor. Meyler’s side effects of drugs. Amsterdam: Elsevier Science B.V., 1996: 1–30.Google Scholar
  13. 13.
    Honig PK, Gillespie BK. Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs. Clin Pharmacokinet 1998; 35(3): 167–71.PubMedCrossRefGoogle Scholar
  14. 14.
    Daly JW. Mechanism of action of caffeine. In: Garattini S, editor. Caffeine, coffee, and health. New York: Raven Press Ltd, 1993: 97–150.Google Scholar
  15. 15.
    Myers MG. Caffeine and cardiac arrhythmias. Ann Intern Med 1991; 1146(2): 147–50.Google Scholar
  16. 16.
    Denaro CP, Brown CR, Jacob PD, et al. Effects of caffeine with repeated dosing. Eur J Clin Pharmacol 1991; 40(3): 273–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Benowitz NL, Jacob III P, Mayan H, et al. Sympathomimetic effects of paraxanthine and caffeine in humans. Clin Pharmacol Ther 1995; 58(6): 684–91.PubMedCrossRefGoogle Scholar
  18. 18.
    Sharp DS, Benowitz NL. Pharmacoepidemiology of the effect of caffeine on blood pressure. Clin Pharmacol Ther 1990; 47(1): 57–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Sawynok J, Yaksh TL. Caffeine as an analgesic adjuvant: a review of pharmacology and mechanisms of action. Pharmacol Rev 1993; 45(1): 43–85.PubMedGoogle Scholar
  20. 20.
    Nehlig A. Are we dependent upon coffee and caffeine? Areview on human and animal data. Neurosci Biobehav Rev 1999; 23(4): 563–76.PubMedCrossRefGoogle Scholar
  21. 21.
    Robertson D, Wade D, Workman R, et al. Tolerance to the humoral and hemodynamic effects of caffeine in man. J Clin Invest 1981; 67(4): 1111–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Shi J, Benowitz NL, Denaro CP, et al. Pharmacokinetic-pharmacodynamic modeling of caffeine: tolerance to pressor effects. Clin Pharmacol Ther 1993; 53(1): 6–14.PubMedCrossRefGoogle Scholar
  23. 23.
    Griffiths RR, Evans SM, Heishman SJ, et al. Low-dose caffeine physical dependence in humans. J Pharmacol Exp Ther 1990; 2556(3): 1123–32.Google Scholar
  24. 24.
    Garrett BE, Griffiths RR. Physical dependence increases the relative reinforcing effects of caffeine versus placebo. Psychopharmacology 1998; 139(3): 195–202.PubMedCrossRefGoogle Scholar
  25. 25.
    Evans SM, Griffiths RR. Caffeine withdrawal: a parametric analysis of caffeine dosing conditions. J Pharmacol Exp Ther 1999; 289(1): 285–94.PubMedGoogle Scholar
  26. 26.
    Hughes JR, Oliveto AH, Bickel WK, et al. Caffeine self-administration and withdrawal: incidence, individual differences and interrelationships. Drug Alcohol Depend 1993; 32(3): 239–46.PubMedCrossRefGoogle Scholar
  27. 27.
    Charney DS, Heninger GR, Jatlow PI. Increased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry 1985; 42(3): 233–43.PubMedCrossRefGoogle Scholar
  28. 28.
    Carrillo JA, Benitez J. CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine. Br J Clin Pharmacol 1996; 41(6): 605–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Garriott JC, Simmons LM, Poklis A, et al. Five cases of fatal overdose from caffeine-containing ‘look-alike’ drugs. J Anal Toxicol 1985; 9(3): 141–3.PubMedGoogle Scholar
  30. 30.
    Dubray C, Paire M, Vanlieferinghen P, et al. Caffeine poisoning in infants resulting from confusion between dosage forms. Aropos of 5 cases [in French]. Therapie 1984; 39(5): 601–4.PubMedGoogle Scholar
  31. 31.
    McGee MB. Caffeine poisoning in a 19-year-old female. J Forensic Sci 1980; 25(1): 29–32.PubMedGoogle Scholar
  32. 32.
    Carrillo JA, Christensen M, Ramos SI, et al. Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva and urine. Ther Drug Monit. In press.Google Scholar
  33. 33.
    Bonati M, Latini R, Tognoni G, et al. Interspecies comparison of in vivo caffeine pharmacokinetics in man, monkey, rabbit, rat, and mouse. Drug Metab Rev 1984; 15(7): 1355–83.PubMedCrossRefGoogle Scholar
  34. 34.
    Zylber-Katz E, Granit L, Levy M. Relationship between caffeine concentrations in plasma and saliva. Clin Pharmacol Ther 1984; 36(1): 133–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Fuhr U, Rost KL. Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva. Pharmacogenetics 1994; 4(3): 109–16.PubMedCrossRefGoogle Scholar
  36. 36.
    Lee TC, Charles BG, Steer PA, et al. Saliva as a valid alternative to serum in monitoring intravenous caffeine treatment for apnea of prematurity. Ther Drug Monit 1996; 18(3): 288–93.PubMedCrossRefGoogle Scholar
  37. 37.
    Somani SM, Gupta P. Caffeine: a new look at an age-old drug. Int J Clin Pharmacol Ther Toxicol 1988; 26(11): 521–33.PubMedGoogle Scholar
  38. 38.
    Lelo A, Miners JO, Robson RA, et al. Quantitative assessment of caffeine partial clearances in man. Br J Clin Pharmacol 1986; 22(2): 183–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Carrillo JA, Benitez J. Caffeine metabolism in a healthy Spanish population: N-acetylator phenotype and oxidation pathways. Clin Pharmacol Ther 1994; 55(3): 293–304.PubMedCrossRefGoogle Scholar
  40. 40.
    Gu L, Gonzalez FJ, Kalow W, et al. Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 1992; 2(2): 73–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Butler MA, Iwasaki M, Guengerich FP, et al. Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc Natl Acad Sci U S A 1989; 86(20): 7696–700.PubMedCrossRefGoogle Scholar
  42. 42.
    Berthou F, Flinois JP, Ratanasavanh D, et al. Evidence for the involvement of several cytochromes P-450 in the first steps of caffeine metabolism by human liver microsomes. Drug Metab Dispos 1991; 19(3): 561–7.PubMedGoogle Scholar
  43. 43.
    Tarrus E, Cami J, Roberts DJ, et al. Accumulation of caffeine in healthy volunteers treated with furafylline. Br J Clin Pharmacol 1987; 236(1): 9–18.CrossRefGoogle Scholar
  44. 44.
    Sesardic D, Boobis AR, Murray BP, et al. Furafylline is a potent and selective inhibitor of cytochrome P450IA2 in man. Br J Clin Pharmacol 1990; 29(6): 651–63.PubMedCrossRefGoogle Scholar
  45. 45.
    Kalow W, Tang BK. The use of caffeine for enzyme assays: a critical appraisal. Clin Pharmacol Ther 1993; 53(5): 503–14.PubMedCrossRefGoogle Scholar
  46. 46.
    Grant DM, Tang BK, Kalow W. A simple test for acetylator phenotype using caffeine. Br J Clin Pharmacol 1984; 17(4): 459–64.PubMedCrossRefGoogle Scholar
  47. 47.
    Arnaud MJ. Metabolism of caffeine and other components of coffee. In: Garattini S, editor. Caffeine, coffee, and health. New York: Raven Press Ltd, 1993: 43–95.Google Scholar
  48. 48.
    Eugster HP, Probst M, Wurgler FE, et al. Caffeine, estradiol, and progesterone interact with human CYP1 Al and CYP1A2; evidence from cDNA-directed expression in Saccharomyces cerevisiae. Drug Metab Dispos 1993; 21(1): 43–9.PubMedGoogle Scholar
  49. 49.
    Tassaneeyakul W, Birkett DJ, Veronese ME, et al. Specificity of substrate and inhibitor probes for human cytochromes P450 1 Al and 1A2. J Pharmacol Exp Ther 1993; 265(1): 401–7.PubMedGoogle Scholar
  50. 50.
    Guengerich FP. Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy. Cancer Res 1988; 48(11): 2946–54.PubMedGoogle Scholar
  51. 51.
    Guengerich FP. Metabolic activation of carcinogens. Pharmacol Ther 1992; 546(1): 17–61.CrossRefGoogle Scholar
  52. 52.
    Shimada T, Yun CH, Yamazaki H, et al. Characterization of human lung microsomal cytochrome P-450 1A1 and its role in the oxidation of chemical carcinogens. Mol Pharmacol 1992; 41(5): 856–64.PubMedGoogle Scholar
  53. 53.
    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): 414–23.PubMedGoogle Scholar
  54. 54.
    Hankinson O. The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 1995; 35: 307–40.PubMedCrossRefGoogle Scholar
  55. 55.
    Guengerich FP, Shimada T, Iwasaki M, et al. Activation of carcinogens by human liver cytochromes P-450. Basic Life Sci 1990; 53: 381–96.PubMedGoogle Scholar
  56. 56.
    Shet MS, McPhaul M, Fisher CW, et al. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos 1997; 25(11): 1298–303.PubMedGoogle Scholar
  57. 57.
    Doser K, Guserle R, Kramer R, et al. Bioequivalence evaluation of two flutamide preparations in healthy female subjects. Arzneimittelforschung 1997; 47(2): 213–7.PubMedGoogle Scholar
  58. 58.
    Venkatakrishnan K, Greenblatt DJ, von Moltke LL, et al. Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4. J Clin Pharmacol 1998; 38(2): 112–21.PubMedGoogle Scholar
  59. 59.
    von Moltke LL, Greenblatt DJ, Shader RI. Clinical pharmacokinetics of antidepressants in the elderly: therapeutic implications. Clin Pharmacokinet 1993; 24(2): 141–60.CrossRefGoogle Scholar
  60. 60.
    Nielsen KK, Flinois JP, Beaune P, et al. The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther 1996; 277(3): 1659–64.PubMedGoogle Scholar
  61. 61.
    Noguchi T, Shimoda K, Takahashi S. Clinical significance of plasma levels of clomipramine, its hydroxylated and desmethylated metabolites: prediction of clinical outcome in mood disorders using discriminant analysis of therapeutic drug monitoring data. J Affect Disord 1993; 29(4): 267–79.PubMedCrossRefGoogle Scholar
  62. 62.
    Carrillo JA, Dahl ML, Svensson JO, et al. Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity. Clin Pharmacol Ther 1996; 60(2): 183–90.PubMedCrossRefGoogle Scholar
  63. 63.
    Spigset O, Granberg K, Hagg S, et al. Relationship between fluvoxamine pharmacokinetics and CYP2D6/CYP2C19 phenotype polymorphisms. Eur J Clin Pharmacol 1997; 52(2): 129–33.PubMedCrossRefGoogle Scholar
  64. 64.
    Koyama E, Chiba K, Tani M, et al. Identification of human cytochrome P450 isoforms involved in the stereoselective metabolism of mianserin enantiomers. J Pharmacol Exp Ther 1996; 278(1): 21–30.PubMedGoogle Scholar
  65. 65.
    Goodnick PJ. Pharmacokinetic optimisation of therapy with newer antidepressants. Clin Pharmacokinet 1994; 27(4): 307–30.PubMedCrossRefGoogle Scholar
  66. 66.
    Lemoine A, Gautier JC, Azoulay D, et al. Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol Pharmacol 1993; 43(5): 827–32.PubMedGoogle Scholar
  67. 67.
    Brøsen K, Gram LF, Klysner R, et al. Steady-state levels of imipramine and its metabolites: significance of dose-dependent kinetics. Eur J Clin Pharmacol 1986; 30(1): 43–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Bertilsson L, Carrillo JA, Dahl ML, et al. Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. Br J Clin Pharmacol 1994; 38(5): 471–3.PubMedCrossRefGoogle Scholar
  69. 69.
    Freeman DJ, Oyewumi LK. Will routine therapeutic drug monitoring have a place in clozapine therapy? Clin Pharmacokinet 1997; 32(2): 93–100.PubMedCrossRefGoogle Scholar
  70. 70.
    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(5): 439–46.PubMedCrossRefGoogle Scholar
  71. 71.
    Shimoda K, Someya T, Morita S, et al. Lower plasma levels of haloperidol in smoking than in nonsmoking schizophrenic patients. Ther Drug Monit 1999; 21(3): 293–6.PubMedCrossRefGoogle Scholar
  72. 72.
    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): 227–63.PubMedCrossRefGoogle Scholar
  73. 73.
    Ring BJ, Catlow J, Lindsay TJ, et al. Identification of the human cytochromes P450 responsible for the in vitro formation of the major oxidative metabolites of the antipsychotic agent olanzapine. J Pharmacol Exp Ther 1996; 276(2): 658–66.PubMedGoogle Scholar
  74. 74.
    Perry PJ, Sanger T, Beasley C. Olanzapine plasma concentrations and clinical response in acutely schizophrenic patients. J Clin Psychopharmacol 1997; 17(6): 472–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Olesen OV, Linnet K. Olanzapine serum concentrations in psychiatric patients given standard doses: the influence of comedication. Ther Drug Monit 1999; 216(1): 87–90.CrossRefGoogle Scholar
  76. 76.
    Carrillo JA, Ramos SI, Herraiz AG, et al. Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients. J Clin Psychopharmacol 1999; 19(6): 494–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Dahl SG. Plasma level monitoring of antipsychotic drugs: clinical utility. Clin Pharmacokinet 1986; 11(1): 36–61.PubMedCrossRefGoogle Scholar
  78. 78.
    Dixon CM, Colthup PV, Serabjit-Singh CJ, et al. Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 1995; 23(11): 1225–30.PubMedGoogle Scholar
  79. 79.
    Roila F, Del Favero A. Ondansetron clinical pharmacokinetics. Clin Pharmacokinet 1995; 29(2): 95–109.PubMedCrossRefGoogle Scholar
  80. 80.
    Imaoka S, Enomoto K, Oda Y, et al. Lidocaine metabolism by human cytochrome P-450s purified from hepatic microsomes: comparison of those with rat hepatic cytochrome P-450s. J Pharmacol Exp Ther 1990; 255(3): 1385–91.PubMedGoogle Scholar
  81. 81.
    Nattel S, Arenal A. Antiarrhythmic prophylaxis after acute myocardial infarction: is lidocaine still useful? Drugs 1993; 45(1): 9–14.PubMedCrossRefGoogle Scholar
  82. 82.
    Nakajima M, Kobayashi K, Shimada N, et al. Involvement of CYP1A2 in mexiletine metabolism. Br J Clin Pharmacol 1998; 466(1): 55–62.Google Scholar
  83. 83.
    Labbé L, Abolfathi Z, Robitaille NM, et al. Stereoselective disposition of the antiarrhythmic agent mexiletine during the concomitant administration of caffeine. Ther Drug Monit 1999; 21(2): 191–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Labbé L, Turgeon J. Clinical pharmacokinetics of mexiletine. Clin Pharmacokinet 1999; 37(5): 361–84.PubMedCrossRefGoogle Scholar
  85. 85.
    Botsch S, Gautier JC, Beaune P, et al. Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites. Mol Pharmacol 1993; 43(1): 120–6.PubMedGoogle Scholar
  86. 86.
    Bryson HM, Palmer KJ, Langtry HD, et al. Propafenone: a reappraisal of its pharmacology, pharmacokinetics and therapeutic use in cardiac arrhythmias. Drugs 1993; 45(1): 85–130.PubMedCrossRefGoogle Scholar
  87. 87.
    Masubuchi Y, Hosokawa S, Horie T, et al. Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes: the role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metab Dispos 1994; 22(6): 909–15.PubMedGoogle Scholar
  88. 88.
    Marathe PH, Shen DD, Nelson WL. Metabolic kinetics of pseudoracemic propranolol in human liver microsomes: enantioselectivity and quinidine inhibition. Drug Metab Dispos 1994; 22(2): 237–47.PubMedGoogle Scholar
  89. 89.
    Yoshimoto K, Echizen H, Chiba K, et al. Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers: N-desisopropylation is mediated mainly by CYP1A2. Br J Clin Pharmacol 1995; 39(4): 421–31.PubMedCrossRefGoogle Scholar
  90. 90.
    Kober S, Spahn-Langguth H, Kurz A, et al. Triamterene hydroxylation in human liver microsomes is mediated by the cytochrome P450 isoform CYP1A2. Naunyn-Schmiedeberg’s Arch Pharmacol 1996; 353 Suppl. 1: R157.Google Scholar
  91. 91.
    Kroemer HK, Gautier JC, Beaune P, et al. Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs’ Arch Pharmacol 1993; 348(3): 332–7.Google Scholar
  92. 92.
    Zhang Z, Fasco MJ, Huang Z, et al. Human cytochromes P4501A1 and P4501A2: R-warfarin metabolism as a probe. Drug Metab Dispos 1995; 23(12): 1339–46.PubMedGoogle Scholar
  93. 93.
    Madden S, Woolf TF, Pool WF, et al. An investigation into the formation of stable, protein-reactive and cytotoxic metabolites from tacrine in vitro. Studies with human and rat liver microsomes. Biochem Pharmacol 1993; 46(1): 13–20.PubMedCrossRefGoogle Scholar
  94. 94.
    Fontana RJ, de Vries TM, Woolf TF, et al. Caffeine based measures of CYP1A2 activity correlate with oral clearance of tacrine in patients with Alzheimer’s disease. Br J Clin Pharmacol 1998; 46(3): 221–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Madden S, Spaldin V, Park BK. Clinical pharmacokinetics of tacrine. Clin Pharmacokinet 1995; 28(6): 449–57.PubMedCrossRefGoogle Scholar
  96. 96.
    Ekström G, Gunnarsson UB. Ropivacaine, a new amide-type local anesthetic agent, is metabolized by cytochromes P450 1A and 3A in human liver microsomes. Drug Metab Dispos 1996; 24(9): 955–61.PubMedGoogle Scholar
  97. 97.
    Emanuelsson BM, Persson J, Sandin S, et al. Intraindividual and interindividual variability in the disposition of the local anesthetic ropivacaine in healthy subjects. Ther Drug Monit 1997; 196(2): 126–31.CrossRefGoogle Scholar
  98. 98.
    Patten CJ, Thomas PE, Guy RL, et al. Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics. Chem Res Toxicol 1993; 6(4): 511–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Kinzig-Schippers M, Fuhr U, Zaigler M, et al. Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2. Clin Pharmacol Ther 1999; 65(3): 262–74.PubMedCrossRefGoogle Scholar
  100. 100.
    Bressolle F, Goncalves F, Gouby A, et al. Pefloxacin clinical pharmacokinetics. Clin Pharmacokinet 1994; 27(6): 418–46.PubMedCrossRefGoogle Scholar
  101. 101.
    Campbell ME, Grant DM, Inaba T, et al. Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes. Drug Metab Dispos 1987; 15(2): 237–49.PubMedGoogle Scholar
  102. 102.
    Scott NR, Stambuk D, Chakraborty J, et al. The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease. Br J Clin Pharmacol 1989; 27(2): 205–13.PubMedCrossRefGoogle Scholar
  103. 103.
    Rasmussen BB, Mäenpää J, Pelkonen O, et al. Selective serotonin reuptake inhibitors and theophylline metabolism in human liver microsomes: potent inhibition by fluvoxamine. Br J Clin Pharmacol 1995; 39(2): 151–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Ha HR, Chen J, Freiburghaus AU, et al. Metabolism of theophylline by cDNA-expressed human cytochromes P-450. Br J Clin Pharmacol 1995; 39(3): 321–6.PubMedCrossRefGoogle Scholar
  105. 105.
    Grant DM, Tang BK, Kalow W Variability in caffeine metabolism. Clin Pharmacol Ther 1983; 33(5): 591–602.PubMedCrossRefGoogle Scholar
  106. 106.
    Kalow W. Variability of caffeine metabolism in humans. Arzneimittelforschung 1985; 35(1A): 319–24.PubMedGoogle Scholar
  107. 107.
    Kadlubar FF, Talaska G, Butler MA, et al. Determination of carcinogenic arylamine N-oxidation phenotype in humans by analysis of caffeine urinary metabolites. In: Mendelsohn ML, Albertini RJ, editors. Mutation and environment. Part B: Metabolism, testing methods, and chromosomes. New York: John Wiley, 1990: 107–14.Google Scholar
  108. 108.
    Rasmussen BB, Brèsen K. Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans. Ther Drug Monit 1996; 18(3): 254–62.PubMedCrossRefGoogle Scholar
  109. 109.
    Tantcheva-Poór I, Zaigler M, Rietbrock S, et al. Estimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test. Pharmacogenetics 1999; 9(2): 131–44.PubMedGoogle Scholar
  110. 110.
    Vistisen K, Loft S, Poulsen HE. Cytochrome P450 IA2 activity in man measured by caffeine metabolism: effect of smoking, broccoli and exercise. Adv Exp Med Biol 1991; 283: 407–11.PubMedCrossRefGoogle Scholar
  111. 111.
    Vistisen K, Poulsen HE, Loft S. Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine. Carcinogenesis 1992; 13(9): 1561–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Le Marchand L, Franke AA, Custer L, et al. Lifestyle and nutritional correlates of cytochrome CYP1A2 activity: inverse associations with plasma lutein and alpha-tocopherol. Pharmacogenetics 1997; 7(1): 11–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Rizzo N, Hispard E, Dolbeault S, et al. Impact of long-term ethanol consumption on CYP1A2 activity. Clin Pharmacol Ther 1997; 62(5): 505–9.PubMedCrossRefGoogle Scholar
  114. 114.
    Fuhr U, Klittich K, Staib AH. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol 1993; 35(4): 431–6.PubMedCrossRefGoogle Scholar
  115. 115.
    Sinha R, Rothman N, Brown ED, et al. Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans. Cancer Res 1994; 54(23): 6154–9.PubMedGoogle Scholar
  116. 116.
    Sinha R, Caporaso N. Heterocyclic amines, cytochrome P4501A2, and N-acetyltransferase: issues involved in incorporating putative genetic susceptibility markers into epidemiological studies. Ann Epidemiol 1997; 7(5): 350–6.PubMedCrossRefGoogle Scholar
  117. 117.
    Denaro CP, Wilson M, Jacob P, et al. The effect of liver disease on urine caffeine metabolite ratios. Clin Pharmacol Ther 1996; 59(6): 624–35.PubMedCrossRefGoogle Scholar
  118. 118.
    Lane JD, Steege JF, Rupp SL, et al. Menstrual cycle effects on caffeine elimination in the human female. Eur J Clin Pharmacol 1992; 43(5): 543–6.PubMedCrossRefGoogle Scholar
  119. 119.
    Aldridge A, Bailey J, Neims AH. The disposition of caffeine during and after pregnancy. Semin Perinatal 1981; 5(4): 310–4.Google Scholar
  120. 120.
    Brown CR, Jacob PD, Wilson M, et al. Changes in rate and pattern of caffeine metabolism after cigarette abstinence. Clin Pharmacol Ther 1988; 43(5): 488–91.PubMedCrossRefGoogle Scholar
  121. 121.
    Kalow W, Tang BK. Caffeine as a metabolic probe: exploration of the enzyme-inducing effect of cigarette smoking. Clin Pharmacol Ther 1991; 49(1): 44–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Waxman DJ. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys 1999; 369(1): 11–23.PubMedCrossRefGoogle Scholar
  123. 123.
    Sinha R, Rothman N. Role of well-done, grilled red meat, heterocyclic amines (HCAs) in the etiology of human cancer. Cancer Lett 1999; 143(2): 189–94.PubMedCrossRefGoogle Scholar
  124. 124.
    Lin JH, Lu AY. Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet 1998; 35(5): 361–90.PubMedCrossRefGoogle Scholar
  125. 125.
    Smith G, Stubbins MJ, Harries LW, et al. Molecular genetics of the human cytochrome P450 monooxygenase superfamily. Xenobiotica 1998; 28(12): 1129–65.PubMedCrossRefGoogle Scholar
  126. 126.
    Carrillo JA, Benitez J. Are antipsychotic drugs potentially chemopreventive agents for cancer? [letter]. Eur J Clin Pharmacol 1999; 55(6): 487–8.PubMedCrossRefGoogle Scholar
  127. 127.
    Relling MV, Lin JS, Ayers GD, et al. Racial and gender differences in N-acetyltransferase, xanthine oxidase, and CYP1A2 activities. Clin Pharmacol Ther 1992; 52(6): 643–58.PubMedCrossRefGoogle Scholar
  128. 128.
    Krul C, Hageman G. Analysis of urinary caffeine metabolites to assess biotransformation enzyme activities by reversedphase high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1998; 709(1): 27–34.PubMedCrossRefGoogle Scholar
  129. 129.
    Bruguerolle B, Toumi M, Faraj F, et al. Influence of the menstrual cycle on theophylline pharmacokinetics in asthmatics. Eur J Clin Pharmacol 1990; 39(1): 59–61.PubMedCrossRefGoogle Scholar
  130. 130.
    Shimada T, Gillam EM, Sutter TR, et al. Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos 1997; 25(5): 617–22.PubMedGoogle Scholar
  131. 131.
    Murray GI, Taylor MC, McFadyen MC, et al. Tumor-specific expression of cytochrome P450 CYP1B1. Cancer Res 1997; 57(14): 3026–31.PubMedGoogle Scholar
  132. 132.
    Fuhr U, Wolff T, Harder S, et al. Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human liver microsomes. Drug Metab Dispos 1990; 186(6): 1005–10.Google Scholar
  133. 133.
    Mandell G, Petri Jr WA. Antimicrobial agents: sulfonamides, trimethoprim-sulfamethoxazole, quinolones, and agents for urinary tract infections. In: Hardman JG, Limbird LE, Molinoff PB, et al., editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: MacGraw Hill, 1996: 1057–72.Google Scholar
  134. 134.
    von Moltke LL, Greenblatt DJ, Duan SX, et al. Phenacetin O-deethylation by human liver microsomes in vitro: inhibition by chemical probes, SSRI antidepressants, nefazodone and venlafaxine. Psychopharmacology Berl 1996; 128(4): 398–407.CrossRefGoogle Scholar
  135. 135.
    Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors: an overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 1997; 32 Suppl. 1: 1–21.PubMedCrossRefGoogle Scholar
  136. 136.
    Brøsen K, Skjelbo E, Rasmussen BB, et al. Fluvoxamine is a potent inhibitor of cytochrome P4501A2. Biochem Pharmacol 1993; 45(6): 1211–4.PubMedCrossRefGoogle Scholar
  137. 137.
    Kobayashi K, Nakajima M, Chiba K, et al. Inhibitory effects of antiarrhythmic drugs on phenacetin O-deethylation catalysed by human CYP1A2. Br J Clin Pharmacol 1998; 45(4): 361–8.PubMedCrossRefGoogle Scholar
  138. 138.
    Nix DE, Zelenitsky SA, Symonds WT, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. In: Reidenberg MM, editor. 93rd Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics; 1992; St. Louis. Clin Pharmacol Ther 1992:183.Google Scholar
  139. 139.
    Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989; 37(3): 279–83.PubMedCrossRefGoogle Scholar
  140. 140.
    Soto J, Sacristan JA, Alsar MJ. Diltiazem treatment impairs theophylline elimination in patients with bronchospastic airway disease. Ther Drug Monit 1994; 166(1): 49–52.CrossRefGoogle Scholar
  141. 141.
    Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987; 33(1): 163–9.PubMedCrossRefGoogle Scholar
  142. 142.
    Nielsen-Kudsk JE, Buhl JS, Johannessen AC. Verapamil-in-duced inhibition of theophylline elimination in healthy humans. Pharmacol Toxicol 1990; 66(2): 101–3.PubMedCrossRefGoogle Scholar
  143. 143.
    Vainer JL, Chouinard G. Interaction between caffeine and clozapine [letter]. J Clin Psychopharmacol 1994; 14(4): 284–5.PubMedCrossRefGoogle Scholar
  144. 144.
    Carrillo JA, Jerling M, Bertilsson L. Comments to ‘interaction between caffeine and clozapine’ [letter]. J Clin Psychopharmacol 1995; 15(5): 376–7.PubMedCrossRefGoogle Scholar
  145. 145.
    Beale MD, Pritchett JT, Kellner CH. Supraventricular tachycardia in a patient receiving ECT, clozapine, and caffeine. Convuls Ther 1994; 10(3): 228–31.PubMedGoogle Scholar
  146. 146.
    Jeppesen U, Loft S, Poulsen HE, et al. A fluvoxamine-caffeine interaction study. Pharmacogenetics 1996; 6(3): 213–22.PubMedCrossRefGoogle Scholar
  147. 147.
    Spigset O. Are adverse drug reactions attributed to fluvoxamine caused by concomitant intake of caffeine? [letter]. Eur J Clin Pharmacol 1998; 54(8): 665–6.PubMedCrossRefGoogle Scholar
  148. 148.
    Carrillo JA, Ramos SI, Herráiz AG, et al. CYP1A2 activity and smoking influence the risk/benefit ratio of olanzapine in schizophrenic patients. In: Balant LP, Benitez J, Dahl SG, et al., editors. Clinical pharmacology in psychiatry: finding the right dose of psychotropic drugs. Brussels: European Commision, COST B1, 1998: 291–5.Google Scholar
  149. 149.
    Iversen SA, Murphy PG, Leakey TE, et al. Unsuspected caffeine toxicity complicating theophylline therapy. Hum Toxicol 1984; 3(6): 509–12.PubMedCrossRefGoogle Scholar
  150. 150.
    Sato J, Nakata H, Owada E, et al. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol 1993; 44(3): 295–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Broughton LJ, Rogers HJ. Decreased systemic clearance of caffeine due to cimetidine. Br J Clin Pharmacol 1981; 12(2): 155–9.PubMedGoogle Scholar
  152. 152.
    May DC, Jarboe CH, VanBakel AB, et al. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982; 31(5): 656–61.PubMedCrossRefGoogle Scholar
  153. 153.
    Brazier JL, Descotes J, Lery N, et al. Inhibition by idrocilamide of the disposition of caffeine. Eur J Clin Pharmacol 1980; 17(1): 37–43.PubMedCrossRefGoogle Scholar
  154. 154.
    Patwardhan RV, Desmond PV, Johnson RF, et al. Impaired elimination of caffeine by oral contraceptive steroids. J Lab Clin Med 1980; 95(4): 603–8.PubMedGoogle Scholar
  155. 155.
    Callahan MM, Robertson RS, Branfman AR, et al. Comparison of caffeine metabolism in three nonsmoking populations after oral administration of radiolabeled caffeine. Drug Metab Dispos 1983; 11(3): 211–7.PubMedGoogle Scholar
  156. 156.
    Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985; 28(4): 425–8.PubMedCrossRefGoogle Scholar
  157. 157.
    Lake CR. Manic psychosis after coffee and phenylpropanolamine. Biol Psychiatry 1991; 30(4): 401–4.PubMedCrossRefGoogle Scholar
  158. 158.
    Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990; 47(6): 675–85.PubMedCrossRefGoogle Scholar
  159. 159.
    Mays DC, Camisa C, Cheney P, et al. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin Pharmacol Ther 1987; 42(6): 621–6.PubMedCrossRefGoogle Scholar
  160. 160.
    McEvoy MT, Stern RS. Psoralens and related compounds in the treatment of psoriasis. Pharmacol Ther 1987; 34(1): 75–97.PubMedCrossRefGoogle Scholar
  161. 161.
    Bendriss EK, Bechtel Y, Bendriss A, et al. Inhibition of caffeine metabolism by 5-methoxypsoralen in patients with psoriasis. Br J Clin Pharmacol 1996; 41(5): 421–4.PubMedCrossRefGoogle Scholar
  162. 162.
    Landes BD, Petite JP, Flouvat B. Clinical pharmacokinetics of lansoprazole. Clin Pharmacokinet 1995; 28(6): 458–70.PubMedCrossRefGoogle Scholar
  163. 163.
    Diaz D, Fabre I, Daujat M, et al. Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology 1990; 99(3): 737–47.PubMedGoogle Scholar
  164. 164.
    Rost KL, Brosicke H, Brockmoller J, et al. Increase of cytochrome P450IA2 activity by omeprazole: evidence by the 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. Clin Pharmacol Ther 1992; 52(2): 170–80.PubMedCrossRefGoogle Scholar
  165. 165.
    Rost KL, Roots I. Accelerated caffeine metabolism after omeprazole treatment is indicated by urinary metabolite ratios: coincidence with plasma clearance and breath test. Clin Pharmacol Ther 1994; 55(4): 402–11.PubMedCrossRefGoogle Scholar
  166. 166.
    Schulz HU, Hartmann M, Steinijans VW, et al. Lack of influence of pantoprazole on the disposition kinetics of theophylline in man. Int J Clin Pharmacol Ther Toxicol 1991; 29(9): 369–75.PubMedGoogle Scholar
  167. 167.
    Staib AH, Stille W, Dietlein G, et al. Interaction between quinolones and caffeine. Drugs 1987; 34 Suppl. 1: 170–4.PubMedCrossRefGoogle Scholar
  168. 168.
    Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989; 33(4): 474–8.PubMedCrossRefGoogle Scholar
  169. 169.
    Nicolau DP, Nightingale CH, Tessier PR, et al. The effect of fleroxacin and ciprofloxacin on the pharmacokinetics of multiple dose caffeine. Drugs 1995; 49 Suppl. 2: 357–9.PubMedCrossRefGoogle Scholar
  170. 170.
    Efthymiopoulos C, Bramer SL, Maroli A, et al. Theophylline and warfarin interaction studies with grepafloxacin. Clin Pharmacokinet 1997; 33 Suppl. 1: 39–46.PubMedCrossRefGoogle Scholar
  171. 171.
    Robson RA, Begg EJ, Atkinson HC, et al. Comparative effects of ciprofloxacin and lomefloxacin on the oxidative metabolism of theophylline. Br J Clin Pharmacol 1990; 29(4): 491–3.PubMedCrossRefGoogle Scholar
  172. 172.
    Robson RA. The effects of quinolones on xanthine pharmacokinetics. Am J Med 1992; 92(4A): 22S–5S.PubMedCrossRefGoogle Scholar
  173. 173.
    Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989; 45(3): 234–40.PubMedCrossRefGoogle Scholar
  174. 174.
    Harder S, Staib AH, Beer C, et al. 4-Quinolones inhibit biotransformation of caffeine. Eur J Clin Pharmacol 1988; 35(6): 651–6.PubMedCrossRefGoogle Scholar
  175. 175.
    Stille W, Harder S, Mieke S, et al. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J Antimicrob Chemother 1987; 20(5): 729–34.PubMedCrossRefGoogle Scholar
  176. 176.
    Barnett G, Segura J, de la Torre R, et al. Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition. Eur J Clin Pharmacol 1990; 39(1): 63–9.PubMedCrossRefGoogle Scholar
  177. 177.
    Cesana M, Broccali G, Imbimbo BP, et al. Effect of single doses of rufloxacin on the disposition of theophylline and caffeine after single administration. Int J Clin Pharmacol Ther Toxicol 1991; 29(4): 133–8.PubMedGoogle Scholar
  178. 178.
    Mahr G, Sorgel F, Granneman GR, et al. Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine. Clin Pharmacokinet 1992; 22 Suppl. 1: 90–7.PubMedCrossRefGoogle Scholar
  179. 179.
    Takagi K, Hasegawa T, Ogura Y, et al. Comparative studies on interaction between theophylline and quinolones. J Asthma 1988; 25(2): 63–71.PubMedCrossRefGoogle Scholar
  180. 180.
    Vincent J, Teng R, Dogolo LC, et al. Effect of trovafloxacin, a new fluoroquinolone antibiotic, on the steady-state pharmacokinetics of theophylline in healthy volunteers. J Antimicrob Chemother 1997; 39 Suppl. B: 81–6.PubMedCrossRefGoogle Scholar
  181. 181.
    Yoovathaworn KC, Sriwatanakul K, Thithapandha A. Influence of caffeine on aspirin pharmacokinetics. Eur J Drug Metab Pharmacokinet 1986; 11(1): 71–6.PubMedCrossRefGoogle Scholar
  182. 182.
    Thithapandha A. Effect of caffeine on the bioavailability and pharmacokinetics of aspirin. J Med Assoc Thai 1989; 72(10): 562–6.PubMedGoogle Scholar
  183. 183.
    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): 311–6.PubMedCrossRefGoogle Scholar
  184. 184.
    Odom-White A, de Leon J. Clozapine levels and caffeine [letter]. J Clin Psychiatry 1996; 57(4): 175–6.PubMedGoogle Scholar
  185. 185.
    Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995; 37(5): 348–50.PubMedCrossRefGoogle Scholar
  186. 186.
    Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988; 49(2): 72–3.PubMedGoogle Scholar
  187. 187.
    Iqbal N, Ahmad B, Janbaz KH, et al. The effect of caffeine on the pharmacokinetics of acetaminophen in man. Biopharm Drug Dispos 1995; 16(6): 481–7.PubMedCrossRefGoogle Scholar
  188. 188.
    Jonkman JH, Sollie FA, Sauter R, et al. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther 1991; 49(3): 248–55.PubMedCrossRefGoogle Scholar
  189. 189.
    Pelkonen O, Mäenpää J, Taavitsainen P, et al. Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica 1998; 28(12): 1203–53.PubMedCrossRefGoogle Scholar
  190. 190.
    Grant DM, Tang BK, Campbell ME, et al. Effect of allopurinol on caffeine disposition in man. Br J Clin Pharmacol 1986; 21(4): 454–8.PubMedCrossRefGoogle Scholar
  191. 191.
    Fuchs P, Haefeli WE, Ledermann HR, et al. Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities. Eur J Clin Pharmacol 1999; 54(11): 869–76.PubMedCrossRefGoogle Scholar
  192. 192.
    Sumbaev VV, Rozanov A. Effect of caffeine on xanthine oxidase activity. Ukr Biokhim Zh 1997; 69(5–6): 196–200.PubMedGoogle Scholar
  193. 193.
    Kalow W, Tang BK. Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 1991; 50: 508–19.PubMedCrossRefGoogle Scholar
  194. 194.
    Carrillo JA, Ramos SI, Agundez JA, et al. Analysis of midazolam and metabolites in plasma by high-performance liquid chromatography: probe of CYP3A. Ther Drug Monit 1998; 206(3): 319–24.CrossRefGoogle Scholar
  195. 195.
    Loi CM, Wei XX, Vestal RE. Inhibition of theophylline metabolism by mexiletine in young male and female nonsmokers. Clin Pharmacol Ther 1991; 49(5): 571–80.PubMedCrossRefGoogle Scholar
  196. 196.
    Kendall JD, Chrymko MM, Cooper BE. Theophylline-mexiletine interaction: a case report. Pharmacotherapy 1992; 12(5): 416–8.PubMedGoogle Scholar
  197. 197.
    Fuhr U, Woodcock BG, Siewert M. Verapamil and drug metabolism by the cytochrome P450 isoform CYP1A2 [letter]. Eur J Clin Pharmacol 1992; 42(4): 463–4.PubMedGoogle Scholar
  198. 198.
    Stringer KA, Mallet J, Clarke M, et al. The effect of three different oral doses of verapamil on the disposition of theophylline. Eur J Clin Pharmacol 1992; 43(1): 35–8.PubMedCrossRefGoogle Scholar
  199. 199.
    De Freitas B, Schwartz G. Effects of caffeine in chronic psychiatric patients. Am J Psychiatry 1979; 136(10): 1337–8.PubMedGoogle Scholar
  200. 200.
    Furlong FW. Possible psychiatric significance of excessive coffee consumption. Can Psychiatr Assoc J 1975; 20(8): 577–83.PubMedGoogle Scholar
  201. 201.
    Greden JF, Fontaine P, Lubetsky M, et al. Anxiety and depression associated with caffeinism among psychiatric inpatients. Am J Psychiatry 1978; 135(8): 963–6.PubMedGoogle Scholar
  202. 202.
    Schreiber GB, Maffeo CE, Robins M, et al. Measurement of coffee and caffeine intake: implications for epidemiologic research. Prev Med 1988; 17(3): 280–94.PubMedCrossRefGoogle Scholar
  203. 203.
    Hughes JR, McHugh P, Holtzman S. Caffeine and schizophrenia. Psychiatr Serv 1998; 49(11): 1415–7.PubMedGoogle Scholar
  204. 204.
    Hyde AP. Response to ‘effects of caffeine on behavior of schizophrenic inpatients’ [comment]. Schizophr Bull 1990; 166(3): 371–2.CrossRefGoogle Scholar
  205. 205.
    Baumann P. Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet 1996; 31(6): 444–69.PubMedCrossRefGoogle Scholar
  206. 206.
    Sproule BA, Naranjo CA, Bremner KE, et al. Selective serotonin reuptake inhibitors and CNS drug interactions. Clin Pharmacokinet 1997; 33(6): 454–71.PubMedCrossRefGoogle Scholar
  207. 207.
    Wagner W, Vause EW. Fluvoxamine: a review of global drugdrug interaction data. Clin Pharmacokinet 1995; 29 Suppl. 1: 26–31; discussion 31–2.CrossRefGoogle Scholar
  208. 208.
    Crewe HK, Lennard MS, Tucker GT, et al. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 1992; 34(3): 262–5.PubMedCrossRefGoogle Scholar
  209. 209.
    Skjelbo E, Brøsen K. Inhibitors of imipramine metabolism by human liver microsomes. Br J Clin Pharmacol 1992; 34(3): 256–61.PubMedCrossRefGoogle Scholar
  210. 210.
    Jeppesen U, Gram LF, Vistisen K, et al. Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. Eur J Clin Pharmacol 1996; 51(1):73–8.PubMedCrossRefGoogle Scholar
  211. 211.
    Xu ZH, Xie HG, Zhou HH. In vivo inhibition of CYP2C19 but not CYP2D6 by fluvoxamine. Br J Clin Pharmacol 1996; 42: 518–21.PubMedCrossRefGoogle Scholar
  212. 212.
    Brøsen K. Differences in interactions of SSRIs. Int Clin Psychopharmacol 1998; 13 Suppl. 5: S45–7.PubMedCrossRefGoogle Scholar
  213. 213.
    Jerling M, Lindstrom L, Bondesson U, et al. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit 1994; 16(4): 368–74.PubMedCrossRefGoogle Scholar
  214. 214.
    Hiemke C, Weigmann H, Härtter S, et al. Elevated levels of clozapine in serum after addition of fluvoxamine [letter]. J Clin Psychopharmacol 1994; 146(4): 279–81.Google Scholar
  215. 215.
    Curry ML, Curry SH, Marroum PJ. Interaction of phenothiazine and related drugs and caffeinated beverages [letter]. DICP 1991; 25(4): 437–8.PubMedGoogle Scholar
  216. 216.
    Hirsch SR. Precipitation of antipsychotic drugs in interaction with coffee or tea [letter]. Lancet 1979; 2(8152): 1130–1.PubMedGoogle Scholar
  217. 217.
    Dahl ML, Bertilsson L. Genetically variable metabolism of antidepressants and neuroleptic drugs in man. Pharmacogenetics 1993; 3(2): 61–70.PubMedCrossRefGoogle Scholar
  218. 218.
    Dahl ML, Lerena A, Bondesson U, et al. Disposition of clozapine in man: lack of association with debrisoquine and S-mephenytoin hydroxylation polymorphisms. Br J Clin Pharmacol 1994; 37: 71–4.PubMedCrossRefGoogle Scholar
  219. 219.
    Simpson GM, Cooper TA. Clozapine plasma levels and convulsions. Am J Psychiatry 1978; 135(1): 99–100.PubMedGoogle Scholar
  220. 220.
    Olesen OV. Therapeutic drug monitoring of clozapine treatment: therapeutic threshold value for serum clozapine concentrations. Clin Pharmacokinet 1998; 34(6): 497–502.PubMedCrossRefGoogle Scholar
  221. 221.
    McCarthy RH. Seizures following smoking cessation in a clozapine responder. Pharmacopsychiatry 1994; 27(5): 210–1.PubMedCrossRefGoogle Scholar
  222. 222.
    Ring BJ, Binkley SN, Vandenbranden M, et al. In vitro interaction of the antipsychotic agent olanzapine with human cytochromes P450 CYP2C9, CYP2C19, CYP2D6 and CYP3A. Br J Clin Pharmacol 1996; 41(3): 181–6.PubMedCrossRefGoogle Scholar
  223. 223.
    Fulton B, Goa KL. Olanzapine. A review of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses. Drugs 1997; 53(2): 281–98.PubMedCrossRefGoogle Scholar
  224. 224.
    Kassahun K, Mattiuz E, Nyhart Jr E, et al. Disposition and biotransformation of the antipsychotic agent olanzapine in humans. Drug Metab Dispos 1997; 25(1): 81–93.PubMedGoogle Scholar
  225. 225.
    Macias WL, Bergstrom RF, Cerimele BJ, et al. Lack of effect of olanzapine on the pharmacokinetics of a single aminophylline dose in healthy men. Pharmacotherapy 1998; 18(6): 1237–48.PubMedGoogle Scholar
  226. 226.
    Thomsen K, Schou M. Renal lithium excretion in man. Am J Physiol 1968; 215(4): 823–7.PubMedGoogle Scholar
  227. 227.
    Bauman JH, Kimelblatt BJ, Caraccio TR, et al. Cimetidine theophylline interaction: report of four patients. Ann Allergy 1982; 48(2): 100–2.PubMedGoogle Scholar
  228. 228.
    Roberts RK, Grice J, McGuffie C. Cimetidine-theophylline interaction in patients with chronic obstructive airways disease. Med J Aust 1984; 140(5): 279–80.PubMedGoogle Scholar
  229. 229.
    Grygiel JJ, Miners JO, Drew R, et al. Differential effects of cimetidine on theophylline metabolic pathways. Eur J Clin Pharmacol 1984; 26(3): 335–40.PubMedCrossRefGoogle Scholar
  230. 230.
    Parker AC, Pritchard P, Preston T, et al. Lack of inhibitory effect of cimetidine on caffeine metabolism in children using the caffeine breath test. Br J Clin Pharmacol 1997; 43(5): 467–70.PubMedCrossRefGoogle Scholar
  231. 231.
    Dal Negro R, Pomari C, Turco P. Famotidine and theophylline pharmacokinetics: an unexpected cimetidine-like interaction in patients with chronic obstructive pulmonary disease. Clin Pharmacokinet 1993; 24(3): 255–8.CrossRefGoogle Scholar
  232. 232.
    Robson RA, Miners JO, Matthews AP, et al. Characterisation of theophylline metabolism by human liver microsomes: inhibition and immunochemical studies. Biochem Pharmacol 1988; 376(9): 1651–9.CrossRefGoogle Scholar
  233. 233.
    Harris RZ, Benet LZ, Schwartz JB. Gender effects in pharmacokinetics and pharmacodynamics. Drugs 1995; 50(2): 222–39.PubMedCrossRefGoogle Scholar
  234. 234.
    Catteau A, Bechtel YC, Poisson N, et al. Apopulation and family study of CYP1A2 using caffeine urinary metabolites. Eur J Clin Pharmacol 1995; 47(5): 423–30.PubMedCrossRefGoogle Scholar
  235. 235.
    Roberts RK, Grice J, McGuffie C, et al. Oral contraceptive steroids impair the elimination of theophylline. J Lab Clin Med 1983; 101(6): 821–5.PubMedGoogle Scholar
  236. 236.
    Balogh A, Klinger G, Henschel L, et al. Influence of ethinylestradiol-containing combination oral contraceptives with gestodene or levonorgestrel on caffeine elimination. Eur J Clin Pharmacol 1995; 48(2): 161–6.PubMedCrossRefGoogle Scholar
  237. 237.
    Laine K, Palovaara S, Tapanainen P, et al. Plasma tacrine concentrations are significantly increased by concomitant hormone replacement therapy. Clin Pharmacol Ther 1999; 666(6): 602–8.Google Scholar
  238. 238.
    Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999; 39(9): 936–40.PubMedCrossRefGoogle Scholar
  239. 239.
    Lee KY, Beilin LJ, Vandongen R. Severe hypertension after ingestion of an appetite suppressant (phenylpropanolamine) with indomethacin. Lancet 1979; 1(8126): 1110–1.PubMedCrossRefGoogle Scholar
  240. 240.
    O’Connell MB, Gross CR. The effect of multiple doses of phenylpropanolamine on the blood pressure of patients whose hypertension was controlled with beta blockers. Pharmacotherapy 1991; 11(5): 376–81.PubMedGoogle Scholar
  241. 241.
    Curi-Pedrosa R, Daujat M, Pichard L, et al. Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture. J Pharmacol Exp Ther 1994; 269(1): 384–92.PubMedGoogle Scholar
  242. 242.
    Nousbaum JB, Berthou F, Carlhant D, et al. Four-week treatment with omeprazole increases the metabolism of caffeine. Am J Gastroenterol 1994; 89(3): 371–5.PubMedGoogle Scholar
  243. 243.
    Dzeletovic N, McGuire J, Daujat M, et al. Regulation of dioxin receptor function by omeprazole. J Biol Chem 1997; 272(19): 12705–13.PubMedCrossRefGoogle Scholar
  244. 244.
    Andersson T. Pharmacokinetics, metabolism and interactions of acid pump inhibitors: focus on omeprazole, lansoprazole and pantoprazole. Clin Pharmacokinet 1996; 316(1): 9–28.CrossRefGoogle Scholar
  245. 245.
    Rizzo N, Padoin C, Palombo S, et al. Omeprazole and lansoprazole are not inducers of cytochrome P4501A2 under conventional therapeutic conditions. Eur J Clin Pharmacol 1996; 49(6): 491–5.PubMedCrossRefGoogle Scholar
  246. 246.
    Taburet AM, Geneve J, Bocquentin M, et al. Theophylline steady state pharmacokinetics is not altered by omeprazole. Eur J Clin Pharmacol 1992; 42(3): 343–5.PubMedCrossRefGoogle Scholar
  247. 247.
    Xiaodong S, Gatti G, Bartoli A, et al. Omeprazole does not enhance the metabolism of phenacetin, a marker of CYP1A2 activity, in healthy volunteers. Ther Drug Monit 1994; 16(3): 248–50.PubMedCrossRefGoogle Scholar
  248. 248.
    Andersson T, Holmberg J, Rohss K, et al. Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole. Br J Clin Pharmacol 1998; 45(4): 369–75.PubMedCrossRefGoogle Scholar
  249. 249.
    Dilger K, Zheng Z, Klotz U. Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline. Br J Clin Pharmacol 1999; 48(3): 438–44.PubMedCrossRefGoogle Scholar
  250. 250.
    Apseloff G, Shepard DR, Chambers MA, et al. Inhibition and induction of theophylline metabolism by 8-methoxypsoralen: in vivo study in rats and humans. Drug Metab Dispos 1990; 18(3): 298–303.PubMedGoogle Scholar
  251. 251.
    Honigsmann H, Jaschke E, Gschnait F, et al. 5-Methoxypsoralen (Bergapten) in photochemotherapy of psoriasis. Br J Dermatol 1979; 101(4): 369–78.PubMedCrossRefGoogle Scholar
  252. 252.
    Tinel M, Belghiti J, Descatoire V, et al. Inactivation of human liver cytochrome P-450 by the drug methoxsalen and other psoralen derivatives. Biochem Pharmacol 1987; 36(6): 951–5.PubMedCrossRefGoogle Scholar
  253. 253.
    Labbe G, Descatoire V, Letteron P, et al. The drug methoxsalen, a suicide substrate for cytochrome P-450, decreases the metabolic activation, and prevents the hepatotoxicity, of carbon tetrachloride in mice. Biochem Pharmacol 1987; 36(6): 907–14.PubMedCrossRefGoogle Scholar
  254. 254.
    Fouin-Fortunet H, Tinel M, Descatoire V, et al. Inactivation of cytochrome P-450 by the drug methoxsalen. J Pharmacol Exp Ther 1986; 2366(1): 237–47.Google Scholar
  255. 255.
    Tantcheva-Poór I, Scharffetter-Kochanek K, Fuhr U. Pronounced effect of oral but not of bath PUVA (methoxsalen plus UVA) on CYP1A2 activity in dermatological patients. In: Dahlqvist R, Offerhaus L, McDevitt D, et al., editors. First Joint Meeting of the German Clinical Pharmacologists; 1999 Jun 10–12; Berlin. Berlin: Springer, 1999: A23.Google Scholar
  256. 256.
    Wijnands WJ, Vree TB, van Herwaarden CL. The influence of quinolone derivatives on theophylline clearance. Br J Clin Pharmacol 1986; 22(6): 677–83.PubMedCrossRefGoogle Scholar
  257. 257.
    Davey PG. Overview of drug interactions with the quinolones. J Antimicrob Chemother 1988; 22 Suppl. C: 97–107.PubMedGoogle Scholar
  258. 258.
    Staib AH, Harder S, Fuhr U, et al. Interaction of quinolones with the theophylline metabolism in man: investigations with lomefloxacin and pipemidic acid. Int J Clin Pharmacol Ther Toxicol 1989; 27(6): 289–3.PubMedGoogle Scholar
  259. 259.
    LeBel M, Vallee F, St-Laurent M. Influence of lomefloxacin on the pharmacokinetics of theophylline. Antimicrob Agents Chemother 1990; 34(6): 1254–6.CrossRefGoogle Scholar
  260. 260.
    Lamp KC, Bailey EM, Rybak MJ. Ofloxacin clinical pharmacokinetics. Clin Pharmacokinet 1992; 22(1): 32–46.PubMedCrossRefGoogle Scholar
  261. 261.
    Marchbanks CR. Drug-drug interactions with fluoroquinolones. Pharmacotherapy 1993; 13(2 Pt 2): 23S–8S.PubMedGoogle Scholar
  262. 262.
    Healy DP, Schoenle JR, Stotka J, et al. Lack of interaction between lomefloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1991; 35(4): 660–4.PubMedCrossRefGoogle Scholar
  263. 263.
    Nix DE, Norman A, Schentag JJ. Effect of lomefloxacin on theophylline pharmacokinetics. Antimicrob Agents Chemother 1989; 33(7): 1006–8.PubMedCrossRefGoogle Scholar
  264. 264.
    Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis 1999; 28(2): 352–64.PubMedCrossRefGoogle Scholar
  265. 265.
    Simpson KJ, Brodie MJ. Convulsions related to enoxacin [letter]. Lancet 1985; 2(8447): 161.PubMedCrossRefGoogle Scholar
  266. 266.
    Christ W. Central nervous system toxicity of quinolones: human and animal findings. J Antimicrob Chemother 1990; 26 Suppl. B: 219–25.PubMedCrossRefGoogle Scholar
  267. 267.
    Birkett DJ, Miners JO. Caffeine renal clearance and urine caffeine concentrations during steady state dosing: implications for monitoring caffeine intake during sports events. Br J Clin Pharmacol 1991; 31(4): 405–8.PubMedCrossRefGoogle Scholar
  268. 268.
    Duthel JM, Vallon JJ, Martin G, et al. Caffeine and sport: role of physical exercise upon elimination. Med Sci Sports Exerc 1991; 23(8): 980–5.PubMedGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  1. 1.Department of Pharmacology and PsychiatryMedical School, University of ExtremaduraBadajozSpain

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