Utilizing PBPK Modeling to Evaluate the Potential of a Significant Drug–Drug Interaction Between Clopidogrel and Dasabuvir: A Scientific Perspective

Clinical Pharmacology and Therapeutics

Volumn 102, Issue 4, 2017, Pages 578-580

  Arya, V ^a   Zhao, P ^a   Reynolds, K S ^a   Mishra, P ^a   Younis, I R ^a  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOPIDOGREL; CYTOCHROME P450 2C8; CYTOCHROME P450 3A4; DASABUVIR; DASABUVIR PLUS OMBITASVIR PLUS PARITAPREVIR PLUS RITONAVIR; GEMFIBROZIL; REPAGLINIDE; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1; ABT-333; ANTIVIRUS AGENT; DRUG COMBINATION; GLUCURONIDE; MACROCYCLIC COMPOUND; RITONAVIR; SULFONAMIDE; TICLOPIDINE; URACIL;

DRUG DISPOSITION; DRUG EXPOSURE; FOOD AND DRUG ADMINISTRATION; HUMAN; LOADING DRUG DOSE; MEDICAL LITERATURE; MULTIPLE DRUG DOSE; NOTE; PRESCRIPTION; PRIORITY JOURNAL; SINGLE DRUG DOSE; ANALOGS AND DERIVATIVES; BIOLOGICAL MODEL; DRUG COMBINATION; DRUG EFFECTS; DRUG INTERACTION; METABOLISM;

ANTIVIRAL AGENTS; CYTOCHROME P-450 CYP2C8; DRUG COMBINATIONS; DRUG INTERACTIONS; GLUCURONIDES; HUMANS; MACROCYCLIC COMPOUNDS; MODELS, BIOLOGICAL; RITONAVIR; SULFONAMIDES; TICLOPIDINE; URACIL;

EID: 85018256225     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1002/cpt.699     Document Type: Note

References (10)

1. Varma, M.V. et al. Mechanistic modeling to predict the transporter- and enzyme-mediated drug-drug interactions of repaglinide. Pharm. Res. 30, 1188–1199 (2013).
2. Ogilvie, B.W. et al. Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions. Drug Metab. Dispos. 34, 191–197 (2006).
3. Polepally, A.R. et al. Drug-drug interactions between the anti-hepatitis C virus 3D regimen of ombitasvir, paritaprevir/ritonavir, and dasabuvir and eight commonly used medications in healthy volunteers. Clin. Pharmacokinet. 55, 1003–1014 (2016).
4. Stark, J.E. Potential for a significant interaction between clopidogrel and dasabuvir. Clin. Infect. Dis. 61, 134–135 (2015).
5. Tornio, A. et al. Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: a phase II metabolite as a perpetrator of drug-drug interactions. Clin. Pharmacol. Ther. 96, 498–507 (2014).
6. Floyd, J.S. et al. A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel. Clin. Pharmacol. Ther. 91, 896–904 (2012).
7. Shebley, M., Fu, W., Badri, P., Bow, D.A.J. & Fischer, V. Physiologically based pharmacokinetic modeling suggests limited drug-drug interaction between clopidogrel and dasabuvir. Clin. Pharmacol. Ther. (in review).
8. Kajosaari, L.I., Laitila, J., Neuvonen, P.J. & Backman, J.T. Metabolism of repaglinide by CYP2C8 and CYP3A4 in vitro: effect of fibrates and rifampicin. Basic Clin. Pharmacol. Toxicol. 97, 249–256 (2005).
9. Kim, S.J. et al. Clarification of the mechanism of clopidogrel-mediated drug-drug interaction in a clinical cassette small-dose study and its prediction based on in vitro information. Drug Metab. Dispos. 44, 1622–1632 (2016).
10. Kimoto, E., Li, R., Scialis, R.J., Lai, Y. & Varma, M.V. Hepatic disposition of gemfibrozil and its major metabolite gemfibrozil 1-O-beta-glucuronide. Mol. Pharm. 12, 3943–3952 (2015).