Physiologically based pharmacokinetic modeling for sequential metabolism: Effect of CYP2C19 genetic polymorphism on clopidogrel and clopidogrel active metabolite pharmacokinetics

Drug Metabolism and Disposition

Volumn 43, Issue 4, 2015, Pages 510-522

  Djebli, Nassim ^a   Fabre, David ^a   Boulenc, Xavier ^a   Fabre, Gérard ^a   Sultan, Eric ^a   Hurbin, Fabrice ^a  

^a SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CLOPI H4; CLOPIDOGREL; CYTOCHROME P450 2C19; DRONEDARONE; DRUG METABOLITE; PLACEBO; UNCLASSIFIED DRUG; 2-OXO-CLOPIDOGREL; AMIODARONE; CYP2C19 PROTEIN, HUMAN; CYTOCHROME P450 2C19 INHIBITOR; TICLOPIDINE;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG METABOLISM; DRUG STRUCTURE; ENZYME ACTIVITY; FEMALE; GENETIC POLYMORPHISM; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; LOADING DRUG DOSE; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHENOTYPE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; ADOLESCENT; ANALOGS AND DERIVATIVES; BIOLOGICAL MODEL; BIOTRANSFORMATION; DRUG INTERACTION; GENETICS; INTESTINE ABSORPTION; METABOLISM; MIDDLE AGED; PHYSIOLOGY; REPRODUCIBILITY; SECONDARY METABOLISM; SINGLE NUCLEOTIDE POLYMORPHISM; TISSUE DISTRIBUTION; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AMIODARONE; AREA UNDER CURVE; BIOTRANSFORMATION; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP2C19; CYTOCHROME P-450 CYP2C19 INHIBITORS; DOUBLE-BLIND METHOD; DRUG INTERACTIONS; HUMANS; INTESTINAL ABSORPTION; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; POLYMORPHISM, SINGLE NUCLEOTIDE; REPRODUCIBILITY OF RESULTS; SECONDARY METABOLISM; TICLOPIDINE; TISSUE DISTRIBUTION; YOUNG ADULT;

EID: 84940368508     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.114.062596     Document Type: Article

References (41)

1. Barrett JS, Della Casa Alberighi O, Läer S, and Meibohm B (2012) Physiologically based pharmacokinetic (PBPK) modeling in children. Clin Pharmacol Ther 92:40-49.
2. Bhatt DL and Topol EJ (2003) Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2:15-28 Review.
3. Boulenc X and Barberan O (2011) Metabolic-based drug-drug interactions prediction, recent approaches for risk assessment along drug development. Drug Metabol Drug Interact 26:147-168.
4. Boulenc X, Djebli N, Shi J., Perrin L, Brian W, Van Horn R, and Hurbin F (2012) Effects of omeprazole and genetic polymorphism of CYP2C19 on the clopidogrel active metabolite. Drug Metab Dispos 40:187-197.
5. Chetty M, Rose RH, Abduljalil K, Patel N., Lu G, Cain T, Jamei M., and Rostami-Hodjegan A (2014) Applications of linking PBPK and PD models to predict the impact of genotypic variability, formulation differences, differences in target binding capacity and target site drug concentrations on drug responses and variability. Front Pharmacol 5:258.
6. Dansette PM, Rosi J, Bertho G., and Mansuy D (2012) Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer. Chem Res Toxicol 25:348-356.
7. Djebli N, Rauch C, Fabre D., and Boulenc X (2009) Quantification of the pharmacokinetic inhibition of a CYP3A4 substrate with low hepatic first pass effect and long terminal half-life; importance of study design and inhibition mechanism: a simulation study. Poster, 16th North American Regional ISSX Meeting, Baltimore. (http://issx.confex.com/issx/16na/webprogram/Paper17095.html).
8. Edginton AN, Schmitt W, and Willmann S (2006) Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clin Pharmacokinet 45:1013-1034.
9. Farid NA, Payne CD, Small D.S., Winters KJ, Ernest CS, 2nd, Brandt JT, Darstein C, Jakubowski JA, and Salazar DE (2007) Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther 81:735-741.
10. Gao H, Yao L, Mathieu H.W., Zhang Y., Maurer TS, Troutman MD, Scott DO, Ruggeri R.B., and Lin J (2008) In silico modeling of nonspecific binding to human liver microsomes. Drug Metab Dispos 36:2130-2135.
11. Holford N (2005) The Visual Predictive Check - Superiority to Standard Diagnostic (Rorschach) Plots. PAGE 14 Absr 738 [http://www.page-meeting.org/default.asp?abstract=738]
12. Hulot JS, Bura A, Villard E., Azizi M, Remones V, Goyenvalle C., Aiach M, Lechat P, and Gaussem P (2006) Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108:2244-2247.
13. Jamei M, Turner D, Yang J., Neuhoff S, Polak S, Rostami-Hodjegan A, and Tucker G (2009) Population-based mechanistic prediction of oral drug absorption. AAPS J 11:225-237.
14. Johnson TN, Boussery K, Rowland-Yeo K, Tucker G.T., and Rostami-Hodjegan A (2010) A semi-mechanistic model to predict the effects of liver cirrhosis on drug clearance. Clin Pharma-cokinet 49:189-206.
15. Karlsson MP, Holford N. (2008) A tutorial on visual predictive checks. PAGE 17 Abstr 1434 [http://www.page-meeting.org/default.asp?abstract=1434]
16. Kazui M, Nishiya Y, Ishizuka T., Hagihara K, Farid NA, Okazaki O, Ikeda T., and Kurihara A (2010) Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 38:92-99.
17. Khalil F and Läer S (2011) Physiologically based pharmacokinetic modeling: methodology, applications, and limitations with a focus on its role in pediatric drug development. J Biomed Biotechnol 2011:907461.
18. Kim KA, Park PW, Hong S.J., and Park JY (2008) The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther 84:236-242.
19. Leong R, Vieira ML, Zhao P, Mulugeta Y., Lee CS, Huang SM, and Burckart GJ (2012) Regulatory experience with physiologically based pharmacokinetic modeling for pediatric drug trials. Clin Pharmacol Ther 91:926-931.
20. Lins R, Broekhuysen J, Necciari J., and Deroubaix X (1999) Pharmacokinetic profile of 14C-labeled clopidogrel. Semin Thromb Hemost 25 (Suppl 2):29-33.
21. Lobell M and Sivarajah V (2003) In silico prediction of aqueous solubility, human plasma protein binding and volume of distribution of compounds from calculated pKa and AlogP98 values. Mol Divers 7:69-87.
22. Lukacova V, Woltosz WS, and Bolger MB (2009) Prediction of modified release pharmacoki-netics and pharmacodynamics from in vitro, immediate release, and intravenous data. AAPS J 11:323-334.
23. Mega JL, Close SL, Wiviott S.D., Shen L., Hockett RD, Brandt JT, Walker JR, Antman E.M., Macias W., and Braunwald E, et al. (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360:354-362.
24. Post TM, Freijer JI, Ploeger B.A., and Danhof M (2008) Extensions to the visual predictive check to facilitate model performance evaluation. J Pharmacokinet Pharmacodyn 35:185-202.
25. Rodgers T and Rowland M (2006) Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions. J Pharm Sci 95:1238-1257.
26. Rodgers T and Rowland M (2007) Mechanistic approaches to volume of distribution predictions: understanding the processes. Pharm Res 24:918-933.
27. Rodgers T, Leahy D, and Rowland M (2005a) Physiologically based pharmacokinetic modeling 1: predicting the tissue distribution of moderate-to-strong bases. J Pharm Sci 94:1259-1276.
28. Rodgers T, Leahy D, and Rowland M (2005b) Tissue distribution of basic drugs: accounting for enantiomeric, compound and regional differences amongst beta-blocking drugs in rat. J Pharm Sci 94:1237-1248.
29. Rostami-Hodjegan A., Amin AM, Spencer E.P., Lennard MS, Tucker GT, and Flanagan RJ (2004) Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients. J Clin Psychopharmacol 24:70-78.
30. Rowland Yeo K., Jamei M, Yang J., Tucker GT, and Rostami-Hodjegan A (2010) Physiologically based mechanistic modelling to predict complex drug-drug interactions involving simultaneous competitive and time-dependent enzyme inhibition by parent compound and its metabolite in both liver and gut - the effect of diltiazem on the time-course of exposure to triazolam. Eur J Pharm Sci 39:298-309.
31. Rowland Yeo K., Walsky RL, Jamei M, Rostami-Hodjegan A, and Tucker GT (2011) Prediction of time-dependent CYP3A4 drug-drug interactions by physiologically based pharmacokinetic modelling: impact of inactivation parameters and enzyme turnover. Eur J Pharm Sci 43:160-173.
32. Sanofi (2014) Summary of Product Characteristics for Multaq®. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/001043/WC500044534.pdf.
33. Simon T, Bhatt DL, Bergougnan L, Farenc C., Pearson K, Perrin L, Vicaut E., Lacreta F, Hurbin F, and Dubar M (2011) Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects. Clin Pharmacol Ther 90:287-295.
34. Thompson CM, Johns DO, Sonawane B, Barton H.A., Hattis D., Tardif R, and Krishnan K (2009) Database for physiologically based pharmacokinetic (PBPK) modeling: physiological data for healthy and health-impaired elderly. J Toxicol Environ Health B Crit Rev 12:1-24.
35. Tuffal G, Roy S, Lavisse M., Brasseur D, Schofield J, Delesque Touchard N, Savi P, Bremond N., Rouchon M-C, and Hurbin F, et al. (2011) An improved method for specific and quantitative determination of the clopidogrel active metabolite isomers in human plasma. Thromb Haemost 105:696-705.
36. Uchimura T, Kato M, Saito T., and Kinoshita H (2010) Prediction of human blood-to-plasma drug concentration ratio. Biopharm Drug Dispos 31:286-297.
37. Umemura K, Furuta T, and Kondo K (2008) The common gene variants of CYP2C19 affect pharmacokinetics and pharmacodynamics in an active metabolite of clopidogrel in healthy subjects. J Thromb Haemost 6:1439-1441.
38. US Food and Drug Administration (2009) MULTAQ® (DRONEDARONE). Briefing Document. Advisory committee meeting of the cardiovascular and renal drugs division of the US Food and Drug Administration. www.fda.gov/downloads/AdvisoryCommittees/⋯/UCM134981.pdf
39. US Food and Drug Administration (2012) Summary Minutes of the Advisory Committee for Pharmaceutical Science and Clinical Pharmacology (http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/UCM306989.pdf).
40. Vieira ML, Zhao P, Berglund E.G., Reynolds KS, Zhang L, Lesko LJ, and Huang SM (2012) Predicting drug interaction potential with a physiologically based pharmacokinetic model: a case study of telithromycin, a time-dependent CYP3A inhibitor. Clin Pharmacol Ther 91:700-708.
41. Yeo KR, Kenny JR, and Rostami-Hodjegan A (2013) Application of in vitro-in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) modelling to investigate the impact of the CYP2C8 polymorphism on rosiglitazone exposure. Eur J Clin Pharmacol 69:1311-1320