Evaluation of the drug interaction potential of aplaviroc, a novel human immunodeficiency virus entry inhibitor, using a modified cooperstown 5 + 1 cocktail

Journal of Clinical Pharmacology
Brendan M JohnsonJoseph S Bertino

Abstract

Aplaviroc is a novel CCR5 antagonist, a class of compounds under investigation as viral entry inhibitors for the treatment of human immunodeficiency virus infection. A modified Cooperstown 5+1 cocktail was used to assess the drug interaction potential of aplaviroc. Fifteen healthy subjects were administered single oral doses of caffeine (CYP1A2), warfarin (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A) alone (reference treatment) and during steady-state administration of aplaviroc (400 mg every 12 hours, test treatment). Metabolite-to-parent area under the plasma concentration versus time curve (AUC) ratios (paraxanthine/caffeine and 5-hydroxyomeprazole/omeprazole), oral clearance (S-warfarin), AUC (midazolam), and metabolite-to-parent urinary excretion ratio (dextrorphan/dextromethorphan) were determined. The test-to-reference treatment ratios (geometric mean ratio and 90% confidence interval) were caffeine, 1.06 (0.97-1.17); S-warfarin, 0.93 (0.76-1.15); omeprazole, 1.07 (0.98-1.16); dextromethorphan, 1.17 (0.97-1.42); midazolam, 1.30 (1.04-1.63). No significant inhibition of CYP1A2, CYP2C9, CYP2C19, or CYP2D6 enzyme activity was observed. Mild inhibition of CYP3A isozymes should not preclude ...Continue Reading

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Citations

Sep 3, 2008·European Journal of Clinical Pharmacology·Silke C MuellerBernd Drewelow
Jul 25, 2013·European Journal of Clinical Pharmacology·Andrew K L GoeyJan H M Schellens
Apr 3, 2009·Current Opinion in HIV and AIDS·William C Olson, Jeffrey M Jacobson
Nov 5, 2014·Journal of Aquatic Animal Health·Zhi-Qiang ChangQian-Qian Zhai
Apr 18, 2009·Current Opinion in HIV and AIDS·Thomas N Kakuda, Monika Schöller-Gyüre
Sep 21, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yuan ShiMei Dong

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