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From evidence based medicine to mechanism based medicine. Reviewing the role of pharmacogenetics

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Abstract

Aim of the review The translation of evidence based medicine to a specific patient presents a considerable challenge. We present by means of the examples nortriptyline, tramadol, clopidogrel, coumarins, abacavir and antipsychotics the discrepancy between available pharmacogenetic information and its implementation in daily clinical practice. Method Literature review. Results A mechanism based approach may be helpful to personalize medicine for the individual patient to which pharmacogenetics may contribute significantly. The lack of consistency in what we accept in bioequivalence and in pharmacogenetics of drug metabolising enzymes is discussed and illustrated with the example of nortriptyline. The impact of pharmacogenetics on examples like tramadol, clopidogrel, coumarins and abacavir is described. Also the present status of the polymorphisms of 5-HT2A and C receptors in antipsychotic-induced weight gain is presented as a pharmacodynamic example with until now a greater distance to clinical implementation. Conclusion The contribution of pharmacogenetics to tailor-made pharmacotherapy, which especially might be of value for patients deviating from the average, has not yet reached the position it seems to deserve.

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References

  1. de Graaf L. Force doctors to a joined consultation. Pharm Weekbl. 2009;45:8–11.

    Google Scholar 

  2. Huang SM, Temple R. Is this the drug or dose for you? Impact and consideration of ethnic factors in global drug development, regulatory review, and clinical practice. Clin Pharmacol Ther. 2008;84(3):287–94.

    Article  PubMed  Google Scholar 

  3. Swen JJ, Wilting I, de Goede AL, Grandia L, Mulder H, Touw DJ, et al. Pharmacogenetics: from bench to byte. Clin Pharmacol Ther. 2008;83(5):781–7.

    Article  PubMed  CAS  Google Scholar 

  4. Weinshilboum R. Inheritance and drug response. N Engl J Med. 2003;348(6):529–37.

    Article  PubMed  Google Scholar 

  5. O’Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009;122(10 Suppl):S22–32.

    Article  PubMed  Google Scholar 

  6. Halling J, Weihe P, Brosen K. CYP2D6 polymorphism in relation to tramadol metabolism: a study of faroese patients. Ther Drug Monit. 2008;30(3):271–5.

    Article  PubMed  CAS  Google Scholar 

  7. Frink MC, Hennies HH, Englberger W, Haurand M, Wilffert B. Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittelforschung. 1996;46(11):1029–36.

    PubMed  CAS  Google Scholar 

  8. Kirchheiner J, Keulen JT, Bauer S, Roots I, Brockmoller J. Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol. 2008;28(1):78–83.

    Article  PubMed  CAS  Google Scholar 

  9. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15.

    Article  PubMed  CAS  Google Scholar 

  10. Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet. 2009;373(9665):723–31.

    Article  PubMed  CAS  Google Scholar 

  11. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354–62.

    Article  PubMed  CAS  Google Scholar 

  12. Holmes DR, Jr., Dehmer GJ, Kaul S, Leifer D, O’Gara PT, Stein CM. ACCF/AHA clopidogrel clinical alert: approaches to the FDA “Boxed Warning”. A report of the American College of Cardiology Foundation Task force on clinical expert consensus documents and the American Heart Association. Circulation 2010.

  13. Roden DM, Altman RB, Benowitz NL, Flockhart DA, Giacomini KM, Johnson JA, et al. Pharmacogenomics: challenges and opportunities. Ann Intern Med. 2006;145(10):749–57.

    Article  PubMed  Google Scholar 

  14. Lieberman JA, Mailman RB, Duncan G, Sikich L, Chakos M, Nichols DE, et al. Serotonergic basis of antipsychotic drug effects in schizophrenia. Biol Psychiatry. 1998;44(11):1099–117.

    Article  PubMed  CAS  Google Scholar 

  15. Reynolds GP, Templeman LA, Zhang ZJ. The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(6):1021–8.

    Article  PubMed  CAS  Google Scholar 

  16. Reynolds GP, Hill MJ, Kirk SL. The 5-HT2C receptor and antipsychoticinduced weight gain–mechanisms and genetics. J Psychopharmacol. 2006;20(4 Suppl):15–8.

    Article  PubMed  Google Scholar 

  17. Arranz MJ, Munro J, Birkett J, Bolonna A, Mancama D, Sodhi M, et al. Pharmacogenetic prediction of clozapine response. Lancet. 2000;355(9215):1615–6.

    Article  PubMed  CAS  Google Scholar 

  18. De Luca V, Mueller DJ, de BA, Kennedy JL. Association of the HTR2C gene and antipsychotic induced weight gain: a meta-analysis. Int J Neuropsychopharmacol. 2007;10(5):697–704.

    Article  PubMed  CAS  Google Scholar 

  19. Mulder H, Franke B, van der van der-Beek AA, Arends J, Wilmink FW, Scheffer H, et al. The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia. J Clin Psychopharmacol. 2007;27(4):338–43.

    Article  PubMed  CAS  Google Scholar 

  20. Mulder H, Franke B, van der Beek AA, Arends J, Wilmink FW, Egberts AC, et al. The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study. Pharmacogenomics J. 2007;7(5):318–24.

    Article  PubMed  CAS  Google Scholar 

  21. Mulder H, Cohen D, Scheffer H, Gispen-de WC, Arends J, Wilmink FW, et al. HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia: a replication study. J Clin Psychopharmacol. 2009;29(1):16–20.

    Article  PubMed  CAS  Google Scholar 

  22. Park YM, Cho JH, Kang SG, Choi JE, Lee SH, Kim L, et al. Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and olanzapine-induced weight gain among Korean schizophrenic patients. J Clin Pharm Ther. 2008;33(1):55–60.

    Article  PubMed  Google Scholar 

  23. Reynolds GP, Zhang Z, Zhang X. Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain. Am J Psychiatry. 2003;160(4):677–9.

    Article  PubMed  Google Scholar 

  24. Templeman LA, Reynolds GP, Arranz B, San L. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet Genomics. 2005;15(4):195–200.

    Article  PubMed  CAS  Google Scholar 

  25. Theisen FM, Hinney A, Bromel T, Heinzel-Gutenbrunner M, Martin M, Krieg JC, et al. Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals. Psychiatr Genet. 2004;14(3):139–42.

    Article  PubMed  Google Scholar 

  26. Becquemont L. Pharmacogenomics of adverse drug reactions: practical applications and perspectives. Pharmacogenomics. 2009;10(6):961–9.

    Article  PubMed  CAS  Google Scholar 

  27. Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe’er I, Floratos A, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009;41(7):816–9.

    Article  PubMed  CAS  Google Scholar 

  28. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004;428(6982):486.

    Article  PubMed  CAS  Google Scholar 

  29. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568–79.

    Article  PubMed  Google Scholar 

  30. Meyer UA. Pharmacogenetics–five decades of therapeutic lessons from genetic diversity. Nat Rev Genet. 2004;5(9):669–76.

    Article  PubMed  CAS  Google Scholar 

  31. van Schie RM, Cascorbi I, Maitland-van der Zee AH. Conference scene: pharmacogenomics at the second PharmSciFair 2009: adverse drug reactions and clinical implementation. Pharmacogenomics. 2009;10(9):1389–91.

    Article  PubMed  Google Scholar 

  32. Wilms EB, Veldkamp RF, van ME, Touw DJ. Partial resistance to acenocoumarol and phenprocoumon caused by enzyme polymorphism. Ned Tijdschr Geneeskd. 2006;150(38):2095–8.

    PubMed  CAS  Google Scholar 

  33. Tan GM, Wu E, Lam YY, Yan BP. Role of warfarin pharmacogenetic testing in clinical practice. Pharmacogenomics. 2010;11(3):439–48.

    Article  PubMed  CAS  Google Scholar 

  34. D’Andrea G, D’Ambrosio RL, Di PP, Chetta M, Santacroce R, Brancaccio V, et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood. 2005;105(2):645–9.

    Article  PubMed  Google Scholar 

  35. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW. Identification of the gene for vitamin K epoxide reductase. Nature. 2004;427(6974):541–4.

    Article  PubMed  CAS  Google Scholar 

  36. Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005;352(22):2285–93.

    Article  PubMed  CAS  Google Scholar 

  37. Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004;427(6974):537–41.

    Article  PubMed  CAS  Google Scholar 

  38. Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009;360(8):753–64.

    Article  PubMed  Google Scholar 

  39. Woodcock J, Lesko LJ. Pharmacogenetics–tailoring treatment for the outliers. N Engl J Med. 2009;360(8):811–3.

    Article  PubMed  CAS  Google Scholar 

  40. Swen JJ, Huizinga TW, Gelderblom H, de Vries EG, Assendelft WJ, Kirchheiner J, et al. Translating pharmacogenomics: challenges on the road to the clinic. PLoS Med. 2007;4(8):e209.

    Article  PubMed  Google Scholar 

  41. Williams JA, Andersson T, Andersson TB, Blanchard R, Behm MO, Cohen N, et al. PhRMA white paper on ADME pharmacogenomics. J Clin Pharmacol. 2008;48(7):849–89.

    Article  PubMed  CAS  Google Scholar 

  42. Check HE. Genome sequencing: the third generation. Nature. 2009;457(7231):768–9.

    Article  Google Scholar 

  43. Abdel-Rahman SM, Leeder JS, Wilson JT, Gaedigk A, Gotschall RR, Medve R, et al. Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on biotransformation. J Clin Pharmacol. 2002;42(1):24–9.

    Article  PubMed  CAS  Google Scholar 

  44. Borlak J, Hermann R, Erb K, Thum T. A rapid and simple CYP2D6 genotyping assay–case study with the analgetic tramadol. Metabolism. 2003;52(11):1439–43.

    Article  PubMed  CAS  Google Scholar 

  45. Enggaard TP, Poulsen L, rendt-Nielsen L, Brosen K, Ossig J, Sindrup SH. The analgesic effect of tramadol after intravenous injection in healthy volunteers in relation to CYP2D6. Anesth Analg. 2006;102(1):146–50.

    Article  PubMed  CAS  Google Scholar 

  46. Paar WD, Poche S, Gerloff J, Dengler HJ. Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol. Eur J Clin Pharmacol. 1997;53(3–4):235–9.

    Article  PubMed  CAS  Google Scholar 

  47. Poulsen L, rendt-Nielsen L, Brosen K, Sindrup SH. The hypoalgesic effect of tramadol in relation to CYP2D6. Clin Pharmacol Ther. 1996;60(6):636–44.

    Article  PubMed  CAS  Google Scholar 

  48. Stamer UM, Lehnen K, Hothker F, Bayerer B, Wolf S, Hoeft A, et al. Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain. 2003;105(1–2):231–8.

    Article  PubMed  CAS  Google Scholar 

  49. Gan SH, Ismail R, Wan Adnan WA, Wan Z. Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects. J Pharm Biomed Anal. 2002;30(2):189–95.

    Article  PubMed  CAS  Google Scholar 

  50. Gleason PP, Frye RF, O’Toole T. Debilitating reaction following the initial dose of tramadol. Ann Pharmacother. 1997;31(10):1150–2.

    PubMed  CAS  Google Scholar 

  51. Aynacioglu AS, Brockmoller J, Bauer S, Sachse C, Guzelbey P, Ongen Z, et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol. 1999;48(3):409–15.

    Article  PubMed  CAS  Google Scholar 

  52. Caraco Y, Muszkat M, Wood AJ. Phenytoin metabolic ratio: a putative marker of CYP2C9 activity in vivo. Pharmacogenetics. 2001;11(7):587–96.

    Article  PubMed  CAS  Google Scholar 

  53. Hennessy S, Leonard CE, Freeman CP, Metlay JP, Chu X, Strom BL, et al. CYP2C9, CYP2C19, and ABCB1 genotype and hospitalization for phenytoin toxicity. J Clin Pharmacol. 2009;49(12):1483–7.

    Article  PubMed  Google Scholar 

  54. Kerb R, Aynacioglu AS, Brockmoller J, Schlagenhaufer R, Bauer S, Szekeres T, et al. The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels. Pharmacogenomics J. 2001;1(3):204–10.

    Article  PubMed  CAS  Google Scholar 

  55. Rosemary J, Surendiran A, Rajan S, Shashindran CH, Adithan C. Influence of the CYP2C9 AND CYP2C19 polymorphisms on phenytoin hydroxylation in healthy individuals from south India. Indian J Med Res. 2006;123(5):665–70.

    PubMed  CAS  Google Scholar 

  56. Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, et al. Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005;102(15):5507–12.

    Article  PubMed  CAS  Google Scholar 

  57. van der Weide WJ, Steijns LS, van Weelden MJ, de HK. The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics. 2001;11(4):287–91.

    Article  PubMed  Google Scholar 

  58. Hashimoto Y, Otsuki Y, Odani A, Takano M, Hattori H, Furusho K, et al. Effect of CYP2C polymorphisms on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Biol Pharm Bull. 1996;19(8):1103–5.

    Article  PubMed  CAS  Google Scholar 

  59. Hung CC, Lin CJ, Chen CC, Chang CJ, Liou HH. Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Ther Drug Monit. 2004;26(5):534–40.

    Article  PubMed  CAS  Google Scholar 

  60. Lee SY, Lee ST, Kim JW. Contributions of CYP2C9/CYP2C19 genotypes and drug interaction to the phenytoin treatment in the Korean epileptic patients in the clinical setting. J Biochem Mol Biol. 2007;40(3):448–52.

    Article  PubMed  CAS  Google Scholar 

  61. Mamiya K, Ieiri I, Shimamoto J, Yukawa E, Imai J, Ninomiya H, et al. The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Epilepsia. 1998;39(12):1317–23.

    Article  PubMed  CAS  Google Scholar 

  62. McCluggage LK, Voils SA, Bullock MR. Phenytoin toxicity due to genetic polymorphism. Neurocrit Care. 2009;10(2):222–4.

    Article  PubMed  Google Scholar 

  63. Ninomiya H, Mamiya K, Matsuo S, Ieiri I, Higuchi S, Tashiro N. Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. Ther Drug Monit. 2000;22(2):230–2.

    Article  PubMed  CAS  Google Scholar 

  64. Odani A, Hashimoto Y, Otsuki Y, Uwai Y, Hattori H, Furusho K, et al. Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Clin Pharmacol Ther. 1997;62(3):287–92.

    Article  PubMed  CAS  Google Scholar 

  65. Soga Y, Nishimura F, Ohtsuka Y, Araki H, Iwamoto Y, Naruishi H, et al. CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic subjects. Life Sci. 2004;74(7):827–34.

    Article  PubMed  CAS  Google Scholar 

  66. Brandolese R, Scordo MG, Spina E, Gusella M, Padrini R. Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Clin Pharmacol Ther. 2001;70(4):391–4.

    PubMed  CAS  Google Scholar 

  67. Jose L, Binila C, Chandy SJ, Mathews JE, Mathews KP. Acenocoumarol and phenytoin toxicity in the presence of CYP2C9 mutation. J Assoc Physicians India. 2008;56:250–2.

    PubMed  Google Scholar 

  68. Kidd RS, Straughn AB, Meyer MC, Blaisdell J, Goldstein JA, Dalton JT. Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics. 1999;9(1):71–80.

    Article  PubMed  CAS  Google Scholar 

  69. Ramasamy K, Narayan SK, Chanolean S, Chandrasekaran A. Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India. Neurol India. 2007;55(4):408–9.

    Article  PubMed  Google Scholar 

  70. Baumann P, Nil R, Souche A, Montaldi S, Baettig D, Lambert S, et al. A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation. J Clin Psychopharmacol. 1996;16(4):307–14.

    Article  PubMed  CAS  Google Scholar 

  71. Herrlin K, Yasui-Furukori N, Tybring G, Widen J, Gustafsson LL, Bertilsson L. Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes. Br J Clin Pharmacol. 2003;56(4):415–21.

    Article  PubMed  CAS  Google Scholar 

  72. Peters EJ, Slager SL, Kraft JB, Jenkins GD, Reinalda MS, McGrath PJ, et al. Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. PLoS One. 2008;3(4):e1872.

    Article  PubMed  Google Scholar 

  73. Rudberg I, Mohebi B, Hermann M, Refsum H, Molden E. Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients. Clin Pharmacol Ther. 2008;83(2):322–7.

    Article  PubMed  CAS  Google Scholar 

  74. Sindrup SH, Brosen K, Hansen MG, Aaes-Jorgensen T, Overo KF, Gram LF. Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Ther Drug Monit. 1993;15(1):11–7.

    Article  PubMed  CAS  Google Scholar 

  75. Yin OQ, Wing YK, Cheung Y, Wang ZJ, Lam SL, Chiu HF, et al. Phenotype-genotype relationship and clinical effects of citalopram in Chinese patients. J Clin Psychopharmacol. 2006;26(4):367–72.

    Article  PubMed  CAS  Google Scholar 

  76. Yu BN, Chen GL, He N, Ouyang DS, Chen XP, Liu ZQ, et al. Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19. Drug Metab Dispos. 2003;31(10):1255–9.

    Article  PubMed  CAS  Google Scholar 

  77. Rudberg I, Hendset M, Uthus LH, Molden E, Refsum H. Heterozygous mutation in CYP2C19 significantly increases the concentration/dose ratio of racemic citalopram and escitalopram (S-citalopram). Ther Drug Monit. 2006;28(1):102–5.

    Article  PubMed  CAS  Google Scholar 

  78. Ohlsson RS, Mwinyi J, Andersson M, Baldwin RM, Pedersen RS, Sim SC, et al. Kinetics of omeprazole and escitalopram in relation to the CYP2C19*17 allele in healthy subjects. Eur J Clin Pharmacol. 2008;64(12):1175–9.

    Article  Google Scholar 

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Conflicts of interest

The division of Pharmacoepidemiology & Clinical Pharmacology employing author Anke-Hilse Maitland-van der Zee, has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private–public funded Top Institute Pharma (http://www.tipharma.nl, includes co-funding from universities, government, and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health.

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Authors and Affiliations

  1. Department of Quality and Patientsafety, Zorggroep Noorderbreedte, P.O. Box 888, 8901 BR, Leeuwarden, The Netherlands

    Bob Wilffert

  2. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

    Jesse Swen

  3. Department of Clinical Pharmacy, Wilhelmina Hospital Assen, Assen, The Netherlands

    Hans Mulder

  4. Apotheek Haagse Ziekenhuizen, P.O. Box 43100, 2504 AC, Den Haag, The Netherlands

    Daan Touw

  5. Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), University of Utrecht, Utrecht, The Netherlands

    Anke-Hilse Maitland-Van der Zee

  6. Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM, Nieuwegein, The Netherlands

    Vera Deneer

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  1. Bob Wilffert
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Correspondence to Bob Wilffert.

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This letter was inadvertently published twice in slightly differing versions. The other version can be found at DOI: http://dx.doi.org/10.1007/s11096-010-9446-1.

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Wilffert, B., Swen, J., Mulder, H. et al. From evidence based medicine to mechanism based medicine. Reviewing the role of pharmacogenetics. Int J Clin Pharm 33, 3–9 (2011). https://doi.org/10.1007/s11096-011-9485-2

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