The effects of modifying in vivo cytochrome P450 3A (CYP3A) activity on etoricoxib pharmacokinetics and of etoricoxib administration on CYP3A activity

Journal of Clinical Pharmacology
Nancy AgrawalKeith Gottesdiener

Abstract

To investigate the influence of modifying in vivo cytochrome P450 3A (CYP3A) activity on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, and of etoricoxib administration on CYP3A activity, a 3-part, randomized, crossover study was conducted in 3 panels of healthy volunteers. In part I, 8 subjects were administered a single dose of 60 mg etoricoxib alone and following daily doses of 400 mg ketoconazole, a known strong inhibitor of CYP3A. In part II, 8 different subjects were administered a single dose of 60 mg etoricoxib alone and following daily doses of 600 mg rifampin, a known strong inducer of CYP3A. In parts I and II, plasma samples were collected following each etoricoxib dose and analyzed for etoricoxib. In part III, 8 different subjects were administered 120 mg etoricoxib or placebo once daily for 11 days, and the erythromycin breath test was administered on day 11 of each period. Coadministration of etoricoxib with daily doses of ketoconazole resulted in an average 43% increase in etoricoxib AUC; based on previous studies, this increase would not be expected to have any clinically meaningful effect. In contrast, coadministration of etoricoxib with daily doses of rifampin had a potentially ...Continue Reading

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Citations

Nov 14, 2007·European Journal of Clinical Pharmacology·Shaojun Shi, Ulrich Klotz
Mar 17, 2009·Journal of Public Health·E Chilet-RosellJ F Horga
Nov 7, 2012·Expert Opinion on Drug Metabolism & Toxicology·Rik J Lories
Oct 31, 2006·Seminars in Cell & Developmental Biology·Sharon BinghamIain P Chessell
Apr 5, 2008·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Sérgio L DalmoraMarcio Fronza
Nov 30, 2018·Current Drug Metabolism·Panjasaram Naidoo, Manoranjenni Chetty

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