The AAPS Journal

, Volume 15, Issue 2, pp 415–426 | Cite as

In Vivo Quantitative Prediction of the Effect of Gene Polymorphisms and Drug Interactions on Drug Exposure for CYP2C19 Substrates

  • Sylvain Goutelle
  • Laurent Bourguignon
  • Nathalie Bleyzac
  • Johanna Berry
  • Fannie Clavel-Grabit
  • Michel Tod
  • Genophar II Working Group
Research Article

Abstract

We present a unified quantitative approach to predict the in vivo alteration in drug exposure caused by either cytochrome P450 (CYP) gene polymorphisms or CYP-mediated drug–drug interactions (DDI). An application to drugs metabolized by CYP2C19 is presented. The metrics used is the ratio of altered drug area under the curve (AUC) to the AUC in extensive metabolizers with no mutation or no interaction. Data from 42 pharmacokinetic studies performed in CYP2C19 genetic subgroups and 18 DDI studies were used to estimate model parameters and predicted AUC ratios by using Bayesian approach. Pharmacogenetic information was used to estimate a parameter of the model which was then used to predict DDI. The method adequately predicted the AUC ratios published in the literature, with mean errors of −0.15 and −0.62 and mean absolute errors of 0.62 and 1.05 for genotype and DDI data, respectively. The approach provides quantitative prediction of the effect of five genotype variants and 10 inhibitors on the exposure to 25 CYP2C19 substrates, including a number of unobserved cases. A quantitative approach for predicting the effect of gene polymorphisms and drug interactions on drug exposure has been successfully applied for CYP2C19 substrates. This study shows that pharmacogenetic information can be used to predict DDI. This may have important implications for the development of personalized medicine and drug development.

KEY WORDS

CYP2C19 drug interactions personalized medicine pharmacogenetics quantitative prediction 

Supplementary material

12248_2012_9431_MOESM1_ESM.doc (40 kb)
ESM 1(DOC 39 kb)
12248_2012_9431_MOESM2_ESM.doc (3.5 mb)
ESM 2(DOC 3563 kb)

REFERENCES

  1. 1.
    Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med. 2005;352(21):2211–21. doi:10.1056/NEJMra032424.PubMedCrossRefGoogle Scholar
  2. 2.
    Ingelman-Sundberg M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci. 2004;25(4):193–200. doi:10.1016/j.tips.2004.02.007.PubMedCrossRefGoogle Scholar
  3. 3.
    Fahmi OA, Hurst S, Plowchalk D, Cook J, Guo F, Youdim K, et al. Comparison of different algorithms for predicting clinical drug–drug interactions, based on the use of CYP3A4 in vitro data: predictions of compounds as precipitants of interaction. Drug Metab Dispos. 2009;37(8):1658–66. doi:10.1124/dmd.108.026252.PubMedCrossRefGoogle Scholar
  4. 4.
    Rostami-Hodjegan A, Tucker GT. Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat Rev Drug Discov. 2007;6(2):140–8. doi:10.1038/nrd2173.PubMedCrossRefGoogle Scholar
  5. 5.
    Ohno Y, Hisaka A, Suzuki H. General framework for the quantitative prediction of CYP3A4-mediated oral drug interactions based on the AUC increase by coadministration of standard drugs. Clin Pharmacokinet. 2007;46(8):681–96.PubMedCrossRefGoogle Scholar
  6. 6.
    Ohno Y, Hisaka A, Ueno M, Suzuki H. General framework for the prediction of oral drug interactions caused by CYP3A4 induction from in vivo information. Clin Pharmacokinet. 2008;47(10):669–80.PubMedCrossRefGoogle Scholar
  7. 7.
    Tod M, Goutelle S, Clavel-Grabit F, Nicolas G, Charpiat B. Quantitative prediction of cytochrome P450 (CYP) 2D6-mediated drug interactions. Clin Pharmacokinet. 2011;50(8):519–30. doi:10.2165/11592620-000000000-00000.PubMedCrossRefGoogle Scholar
  8. 8.
    US Food and Drug Administration. Guidance for industry. Clinical pharmacogenomics: premarketing evaluation in early phase clinical studies. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM243702.pdf (2011). Accessed 28 June 2012.
  9. 9.
    Tod M, Goutelle S, Gagnieu MC. Genotype-based quantitative prediction of drug exposure for drugs metabolized by CYP2D6. Clin Pharmacol Ther. 2011;90(4):582–7. doi:10.1038/clpt.2011.147.PubMedCrossRefGoogle Scholar
  10. 10.
    Tomalik-Scharte D, Lazar A, Fuhr U, Kirchheiner J. The clinical role of genetic polymorphisms in drug-metabolizing enzymes. Pharmacogenomics J. 2008;8(1):4–15. doi:10.1038/sj.tpj.6500462.PubMedCrossRefGoogle Scholar
  11. 11.
    The Human Cytochrome P450 (CYP) Allele Nomenclature Database. http://www.cypalleles.ki.se/. Accessed 28 June 2012.
  12. 12.
    Baldwin RM, Ohlsson S, Pedersen RS, Mwinyi J, Ingelman-Sundberg M, Eliasson E, et al. Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers. Br J Clin Pharmacol. 2008;65(5):767–74. doi:10.1111/j.1365-2125.2008.03104.x.PubMedCrossRefGoogle Scholar
  13. 13.
    Spiegelhalter D, Thomas A, Best N, Lunn D. Winbugs 1.4.3 user manual. Cambridge: MRC Biostatistics Unit IoPH. 2007.Google Scholar
  14. 14.
    Congdon P. Bayesian statistical modelling. Chichester: Wiley; 2001.Google Scholar
  15. 15.
    Steimer W, Zopf K, von Amelunxen S, Pfeiffer H, Bachofer J, Popp J, et al. Allele-specific change of concentration and functional gene dose for the prediction of steady-state serum concentrations of amitriptyline and nortriptyline in CYP2C19 and CYP2D6 extensive and intermediate metabolizers. Clin Chem. 2004;50(9):1623–33. doi:10.1373/clinchem.2003.030825.PubMedCrossRefGoogle Scholar
  16. 16.
    Fudio S, Borobia AM, Pinana E, Ramirez E, Tabares B, Guerra P, et al. Evaluation of the influence of sex and CYP2C19 and CYP2D6 polymorphisms in the disposition of citalopram. Eur J Pharmacol. 2010;626(2–3):200–4. doi:10.1016/j.ejphar.2009.10.007.PubMedCrossRefGoogle Scholar
  17. 17.
    Yoo HD, Park SA, Cho HY, Lee YB. Influence of CYP3A and CYP2C19 genetic polymorphisms on the pharmacokinetics of cilostazol in healthy subjects. Clin Pharmacol Ther. 2009;86(3):281–4. doi:10.1038/clpt.2009.90.PubMedCrossRefGoogle Scholar
  18. 18.
    Yokono A, Morita S, Someya T, Hirokane G, Okawa M, Shimoda K. The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients. J Clin Psychopharmacol. 2001;21(6):549–55.PubMedCrossRefGoogle Scholar
  19. 19.
    Kim KA, Park PW, Hong SJ, Park JY. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther. 2008;84(2):236–42. doi:10.1038/clpt.2008.20.PubMedCrossRefGoogle Scholar
  20. 20.
    Qin XP, Xie HG, Wang W, He N, Huang SL, Xu ZH, et al. Effect of the gene dosage of CgammaP2C19 on diazepam metabolism in Chinese subjects. Clin Pharmacol Ther. 1999;66(6):642–6. doi:10.1016/S0009-9236(99)90075-9.PubMedGoogle Scholar
  21. 21.
    Noehr-Jensen L, Zwisler ST, Larsen F, Sindrup SH, Damkier P, Nielsen F, et al. Impact of CYP2C19 phenotypes on escitalopram metabolism and an evaluation of pupillometry as a serotonergic biomarker. Eur J Clin Pharmacol. 2009;65(9):887–94. doi:10.1007/s00228-009-0657-0.PubMedCrossRefGoogle Scholar
  22. 22.
    Liu ZQ, Cheng ZN, Huang SL, Chen XP, Ou-Yang DS, Jiang CH, et al. Effect of the CYP2C19 oxidation polymorphism on fluoxetine metabolism in Chinese healthy subjects. Br J Clin Pharmacol. 2001;52(1):96–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Shao H, Ren XM, Liu NF, Chen GM, Li WL, Zhai ZH, et al. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics and pharmacodynamics of gliclazide in healthy Chinese Han volunteers. J Clin Pharm Ther. 2010;35(3):351–60. doi:10.1111/j.1365-2710.2009.01134.x.PubMedCrossRefGoogle Scholar
  24. 24.
    Ieiri I, Kishimoto Y, Okochi H, Momiyama K, Morita T, Kitano M, et al. Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism. Eur J Clin Pharmacol. 2001;57(6–7):485–92.PubMedGoogle Scholar
  25. 25.
    Miura M, Tada H, Yasui-Furukori N, Uno T, Sugawara K, Tateishi T, et al. Enantioselective disposition of lansoprazole in relation to CYP2C19 genotypes in the presence of fluvoxamine. Br J Clin Pharmacol. 2005;60(1):61–8. doi:10.1111/j.1365-2125.2005.02381.x.PubMedCrossRefGoogle Scholar
  26. 26.
    Kobayashi K, Morita J, Chiba K, Wanibuchi A, Kimura M, Irie S, et al. Pharmacogenetic roles of CYP2C19 and CYP2B6 in the metabolism of R- and S-mephobarbital in humans. Pharmacogenetics. 2004;14(8):549–56.PubMedCrossRefGoogle Scholar
  27. 27.
    Yu KS, Yim DS, Cho JY, Park SS, Park JY, Lee KH, et al. Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19. Clin Pharmacol Ther. 2001;69(4):266–73. doi:10.1067/mcp.2001.114231.PubMedCrossRefGoogle Scholar
  28. 28.
    Damle BD, Uderman H, Biswas P, Crownover P, Lin C, Glue P. Influence of CYP2C19 polymorphism on the pharmacokinetics of nelfinavir and its active metabolite. Br J Clin Pharmacol. 2009;68(5):682–9. doi:10.1111/j.1365-2125.2009.03499.x.PubMedCrossRefGoogle Scholar
  29. 29.
    Shirai N, Furuta T, Moriyama Y, Okochi H, Kobayashi K, Takashima M, et al. Effects of CYP2C19 genotypic differences in the metabolism of omeprazole and rabeprazole on intragastric pH. Aliment Pharmacol Ther. 2001;15(12):1929–37.PubMedCrossRefGoogle Scholar
  30. 30.
    Hunfeld NG, Mathot RA, Touw DJ, van Schaik RH, Mulder PG, Franck PF, et al. Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians. Br J Clin Pharmacol. 2008;65(5):752–60. doi:10.1111/j.1365-2125.2007.03094.x.PubMedCrossRefGoogle Scholar
  31. 31.
    Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM. Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003;59(5–6):429–42. doi:10.1007/s00228-003-0636-9.PubMedCrossRefGoogle Scholar
  32. 32.
    Coller JK, Somogyi AA, Bochner F. Association between CYP2C19 genotype and proguanil oxidative polymorphism. Br J Clin Pharmacol. 1997;43(6):659–60.PubMedCrossRefGoogle Scholar
  33. 33.
    Rudberg I, Hermann M, Refsum H, Molden E. Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients. Eur J Clin Pharmacol. 2008;64(12):1181–8. doi:10.1007/s00228-008-0533-3.PubMedCrossRefGoogle Scholar
  34. 34.
    Kim KA, Song WK, Park JY. Association of CYP2B6, CYP3A5, and CYP2C19 genetic polymorphisms with sibutramine pharmacokinetics in healthy Korean subjects. Clin Pharmacol Ther. 2009;86(5):511–8. doi:10.1038/clpt.2009.145.PubMedCrossRefGoogle Scholar
  35. 35.
    Kirchheiner J, Muller G, Meineke I, Wernecke KD, Roots I, Brockmoller J. Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. J Clin Psychopharmacol. 2003;23(5):459–66. doi:10.1097/01.jcp.0000088909.24613.92.PubMedCrossRefGoogle Scholar
  36. 36.
    Scholz I, Oberwittler H, Riedel KD, Burhenne J, Weiss J, Haefeli WE, et al. Pharmacokinetics, metabolism and bioavailability of the triazole antifungal agent voriconazole in relation to CYP2C19 genotype. Br J Clin Pharmacol. 2009;68(6):906–15. doi:10.1111/j.1365-2125.2009.03534.x.PubMedCrossRefGoogle Scholar
  37. 37.
    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. doi:10.1124/dmd.31.10.1255.PubMedCrossRefGoogle Scholar
  38. 38.
    Ohlsson Rosenborg S, 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. doi:10.1007/s00228-008-0529-z.PubMedCrossRefGoogle Scholar
  39. 39.
    Zhang Y, Si D, Chen X, Lin N, Guo Y, Zhou H, et al. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects. Br J Clin Pharmacol. 2007;64(1):67–74. doi:10.1111/j.1365-2125.2007.02846.x.PubMedCrossRefGoogle Scholar
  40. 40.
    Katsuki H, Nakamura C, Arimori K, Fujiyama S, Nakano M. Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects. Eur J Clin Pharmacol. 1997;52(5):391–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Itagaki F, Homma M, Yuzawa K, Nishimura M, Naito S, Ueda N, et al. Effect of lansoprazole and rabeprazole on tacrolimus pharmacokinetics in healthy volunteers with CYP2C19 mutations. J Pharm Pharmacol. 2004;56(8):1055–9. doi:10.1211/0022357043914.PubMedCrossRefGoogle Scholar
  42. 42.
    Qiao HL, Hu YR, Tian X, Jia LJ, Gao N, Zhang LR, et al. Pharmacokinetics of three proton pump inhibitors in Chinese subjects in relation to the CYP2C19 genotype. Eur J Clin Pharmacol. 2006;62(2):107–12. doi:10.1007/s00228-005-0063-1.PubMedCrossRefGoogle Scholar
  43. 43.
    Zalloum I, Hakooz N, Arafat T. Genetic polymorphism of CYP2C19 in a Jordanian population: influence of allele frequencies of CYP2C19*1 and CYP2C19*2 on the pharmacokinetic profile of lansoprazole. Mol Biol Rep. 2012;39(4):4195–200. doi:10.1007/s11033-011-1204-5.PubMedCrossRefGoogle Scholar
  44. 44.
    Sakai T, Aoyama N, Kita T, Sakaeda T, Nishiguchi K, Nishitora Y, et al. CYP2C19 genotype and pharmacokinetics of three proton pump inhibitors in healthy subjects. Pharm Res. 2001;18(6):721–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Chen BL, Chen Y, Tu JH, Li YL, Zhang W, Li Q, et al. Clopidogrel inhibits CYP2C19-dependent hydroxylation of omeprazole related to CYP2C19 genetic polymorphisms. J Clin Pharmacol. 2009;49(5):574–81. doi:10.1177/0091270009333016.PubMedCrossRefGoogle Scholar
  46. 46.
    Uno T, Niioka T, Hayakari M, Yasui-Furukori N, Sugawara K, Tateishi T. Absolute bioavailability and metabolism of omeprazole in relation to CYP2C19 genotypes following single intravenous and oral administrations. Eur J Clin Pharmacol. 2007;63(2):143–9. doi:10.1007/s00228-006-0251-7.PubMedCrossRefGoogle Scholar
  47. 47.
    Yasui-Furukori N, Takahata T, Nakagami T, Yoshiya G, Inoue Y, Kaneko S, et al. Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes. Br J Clin Pharmacol. 2004;57(4):487–94. doi:10.1111/j.1365-2125.2003.02047.x.PubMedCrossRefGoogle Scholar
  48. 48.
    Cho JY, Yu KS, Jang IJ, Yang BH, Shin SG, Yim DS. Omeprazole hydroxylation is inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19. Br J Clin Pharmacol. 2002;53(4):393–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Hunfeld NG, Touw DJ, Mathot RA, Mulder PG, Van Schaik RH, Kuipers EJ, et al. A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism. Aliment Pharmacol Ther. 2010;31(1):150–9. doi:10.1111/j.1365-2036.2009.04150.x.PubMedCrossRefGoogle Scholar
  50. 50.
    Niioka T, Uno T, Yasui-Furukori N, Shimizu M, Sugawara K, Tateishi T. Identification of the time-point which gives a plasma rabeprazole concentration that adequately reflects the area under the concentration–time curve. Eur J Clin Pharmacol. 2006;62(10):855–61. doi:10.1007/s00228-006-0184-1.PubMedCrossRefGoogle Scholar
  51. 51.
    Horai Y, Kimura M, Furuie H, Matsuguma K, Irie S, Koga Y, et al. Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes. Aliment Pharmacol Ther. 2001;15(6):793–803.PubMedCrossRefGoogle Scholar
  52. 52.
    Shimizu M, Uno T, Yasui-Furukori N, Sugawara K, Tateishi T. Effects of clarithromycin and verapamil on rabeprazole pharmacokinetics between CYP2C19 genotypes. Eur J Clin Pharmacol. 2006;62(8):597–603. doi:10.1007/s00228-006-0152-9.PubMedCrossRefGoogle Scholar
  53. 53.
    Wang G, Lei HP, Li Z, Tan ZR, Guo D, Fan L, et al. The CYP2C19 ultra-rapid metabolizer genotype influences the pharmacokinetics of voriconazole in healthy male volunteers. Eur J Clin Pharmacol. 2009;65(3):281–5. doi:10.1007/s00228-008-0574-7.PubMedCrossRefGoogle Scholar
  54. 54.
    Weiss J, Ten Hoevel MM, Burhenne J, Walter-Sack I, Hoffmann MM, Rengelshausen J, et al. CYP2C19 genotype is a major factor contributing to the highly variable pharmacokinetics of voriconazole. J Clin Pharmacol. 2009;49(2):196–204. doi:10.1177/0091270008327537.PubMedCrossRefGoogle Scholar
  55. 55.
    Shi HY, Yan J, Zhu WH, Yang GP, Tan ZR, Wu WH, et al. Effects of erythromycin on voriconazole pharmacokinetics and association with CYP2C19 polymorphism. Eur J Clin Pharmacol. 2010;66(11):1131–6. doi:10.1007/s00228-010-0869-3.PubMedCrossRefGoogle Scholar
  56. 56.
    Mikus G, Schowel V, Drzewinska M, Rengelshausen J, Ding R, Riedel KD, et al. Potent cytochrome P450 2C19 genotype-related interaction between voriconazole and the cytochrome P450 3A4 inhibitor ritonavir. Clin Pharmacol Ther. 2006;80(2):126–35. doi:10.1016/j.clpt.2006.04.004.PubMedCrossRefGoogle Scholar
  57. 57.
    Martis S, Peter I, Hulot JS, Kornreich R, Desnick RJ, Scott SA. Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes. Pharmacogenomics J. 2012. doi:10.1038/tpj.2012.10.
  58. 58.
    Saari TI, Laine K, Bertilsson L, Neuvonen PJ, Olkkola KT. Voriconazole and fluconazole increase the exposure to oral diazepam. Eur J Clin Pharmacol. 2007;63(10):941–9. doi:10.1007/s00228-007-0350-0.PubMedCrossRefGoogle Scholar
  59. 59.
    Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43(4):412–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Wood N, Tan K, Purkins L, Layton G, Hamlin J, Kleinermans D, et al. Effect of omeprazole on the steady-state pharmacokinetics of voriconazole. Br J Clin Pharmacol. 2003;56 Suppl 1:56–61.PubMedCrossRefGoogle Scholar
  61. 61.
    Angiolillo DJ, Gibson CM, Cheng S, Ollier C, Nicolas O, Bergougnan L, et al. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther. 2011;89(1):65–74. doi:10.1038/clpt.2010.219.PubMedCrossRefGoogle Scholar
  62. 62.
    Tateishi T, Kumai T, Watanabe M, Nakura H, Tanaka M, Kobayashi S. Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism. Br J Clin Pharmacol. 1999;47(4):454–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Bae JW, Jang CG, Lee SY. Effects of clopidogrel on the pharmacokinetics of sibutramine and its active metabolites. J Clin Pharmacol. 2011;51(12):1704–11. doi:10.1177/0091270010388651.PubMedCrossRefGoogle Scholar
  64. 64.
    Kang BC, Yang CQ, Cho HK, Suh OK, Shin WG. Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers. Biopharm Drug Dispos. 2002;23(2):77–81.PubMedCrossRefGoogle Scholar
  65. 65.
    Yasui-Furukori N, Saito M, Uno T, Takahata T, Sugawara K, Tateishi T. Effects of fluvoxamine on lansoprazole pharmacokinetics in relation to CYP2C19 genotypes. J Clin Pharmacol. 2004;44(11):1223–9. doi:10.1177/0091270004269015.PubMedCrossRefGoogle Scholar
  66. 66.
    Uno T, Shimizu M, Yasui-Furukori N, Sugawara K, Tateishi T. Different effects of fluvoxamine on rabeprazole pharmacokinetics in relation to CYP2C19 genotype status. Br J Clin Pharmacol. 2006;61(3):309–14. doi:10.1111/j.1365-2125.2005.02556.x.PubMedCrossRefGoogle Scholar
  67. 67.
    Perucca E, Gatti G, Cipolla G, Spina E, Barel S, Soback S, et al. Inhibition of diazepam metabolism by fluvoxamine: a pharmacokinetic study in normal volunteers. Clin Pharmacol Ther. 1994;56(5):471–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Fang AF, Damle BD, LaBadie RR, Crownover PH, Hewlett Jr D, Glue PW. Significant decrease in nelfinavir systemic exposure after omeprazole coadministration in healthy subjects. Pharmacotherapy. 2008;28(1):42–50. doi:10.1592/phco.28.1.42.PubMedCrossRefGoogle Scholar
  69. 69.
    Caraco Y, Tateishi T, Wood AJ. Interethnic difference in omeprazole’s inhibition of diazepam metabolism. Clin Pharmacol Ther. 1995;58(1):62–72. doi:10.1016/0009-9236(95)90073-X.PubMedCrossRefGoogle Scholar
  70. 70.
    Funck-Brentano C, Becquemont L, Lenevu A, Roux A, Jaillon P, Beaune P. Inhibition by omeprazole of proguanil metabolism: mechanism of the interaction in vitro and prediction of in vivo results from the in vitro experiments. J Pharmacol Exp Ther. 1997;280(2):730–8.PubMedGoogle Scholar
  71. 71.
    Furuta T, Sugimoto M, Shirai N, Ishizaki T. CYP2C19 pharmacogenomics associated with therapy of Helicobacter pylori infection and gastro-esophageal reflux diseases with a proton pump inhibitor. Pharmacogenomics. 2007;8(9):1199–210. doi:10.2217/14622416.8.9.1199.PubMedCrossRefGoogle Scholar
  72. 72.
    Zabalza M, Subirana I, Sala J, Lluis-Ganella C, Lucas G, Tomas M, et al. Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart. 2012;98(2):100–8. doi:10.1136/hrt.2011.227652.PubMedCrossRefGoogle Scholar
  73. 73.
    Kita T, Sakaeda T, Baba T, Aoyama N, Kakumoto M, Kurimoto Y, et al. Different contribution of CYP2C19 in the in vitro metabolism of three proton pump inhibitors. Biol Pharm Bull. 2003;26(3):386–90.PubMedCrossRefGoogle Scholar
  74. 74.
    von Moltke LL, Greenblatt DJ, Giancarlo GM, Granda BW, Harmatz JS, Shader RI. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab Dispos. 2001;29(8):1102–9.Google Scholar
  75. 75.
    Soars MG, Gelboin HV, Krausz KW, Riley RJ. A comparison of relative abundance, activity factor and inhibitory monoclonal antibody approaches in the characterization of human CYP enzymology. Br J Clin Pharmacol. 2003;55(2):175–81.PubMedCrossRefGoogle Scholar
  76. 76.
    Venkatakrishnan K, von Moltke LL, Court MH, Harmatz JS, Crespi CL, Greenblatt DJ. Comparison between cytochrome P450 (CYP) content and relative activity approaches to scaling from cDNA-expressed CYPs to human liver microsomes: ratios of accessory proteins as sources of discrepancies between the approaches. Drug Metab Dispos. 2000;28(12):1493–504.PubMedGoogle Scholar
  77. 77.
    Ito K, Brown HS, Houston JB. Database analyses for the prediction of in vivo drug–drug interactions from in vitro data. Br J Clin Pharmacol. 2004;57(4):473–86. doi:10.1111/j.1365-2125.2003.02041.x.PubMedCrossRefGoogle Scholar
  78. 78.
    Obach RS, Walsky RL, Venkatakrishnan K, Gaman EA, Houston JB, Tremaine LM. The utility of in vitro cytochrome P450 inhibition data in the prediction of drug–drug interactions. J Pharmacol Exp Ther. 2006;316(1):336–48. doi:10.1124/jpet.105.093229.PubMedCrossRefGoogle Scholar
  79. 79.
    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.PubMedCrossRefGoogle Scholar
  80. 80.
    Wilkins JJ, Langdon G, McIlleron H, Pillai G, Smith PJ, Simonsson US. Variability in the population pharmacokinetics of isoniazid in South African tuberculosis patients. Br J Clin Pharmacol. 2011;72(1):51–62. doi:10.1111/j.1365-2125.2011.03940.x.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Sylvain Goutelle
    • 1
    • 2
    • 3
    • 6
  • Laurent Bourguignon
    • 1
    • 3
  • Nathalie Bleyzac
    • 3
    • 4
  • Johanna Berry
    • 5
  • Fannie Clavel-Grabit
    • 5
  • Michel Tod
    • 2
    • 5
  • Genophar II Working Group
  1. 1.Service Pharmaceutique, Groupement Hospitalier de GériatrieHospices Civils de LyonLyonFrance
  2. 2.ISPB—Faculté de Pharmacie de LyonUniversité Lyon 1, Université de LyonLyonFrance
  3. 3.Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558Université Lyon 1VilleurbanneFrance
  4. 4.Institut d’Hématologie et d’Oncologie PédiatriqueLyonFrance
  5. 5.Service PharmaceutiqueHôpital de la Croix-Rousse, Hospices Civils de LyonLyonFrance
  6. 6.PharmacieHôpital Pierre GarraudLyonFrance

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