Maribavir Pharmacokinetics and the Effects of Multiple-Dose Maribavir on Cytochrome P450 (CYP) 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A, N-Acetyltransferase-2, and Xanthine Oxidase Activities in Healthy Adults

摘要

Maribavir (1263W94, VP-41263) is an oral anticytomegalovirus agent under clinical development. The pharmacokinetics and safety of maribavir and the effects of maribavir on the activities of cytochrome P450 (CYP) 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) were evaluated in a randomized, double-blind, placebo-controlled study. Twenty healthy subjects received a five-drug phenotyping cocktail of caffeine (CYP 1A2, NAT-2, XO), warfarin plus vitamin K (CYP 2C9), omeprazole (CYP 2C19), dextromethorphan (CYP 2D6), and midazolam (CYP 3A) 4 days before and after 7 days of treatment with maribavir at 400 mg twice daily (16 subjects) or placebo (4 subjects) for 10 days. Maribavir did not affect the CYP 1A2, CYP 2C9, CYP 3A, NAT-2, or XO activities. Bioequivalence was not demonstrated for CYP 2C19 and CYP 2D6, suggesting a decrease or inhibition of CYP 2C19 and CYP 2D6 activities. The pharmacokinetics of maribavir following a single dose and after 10 days of treatment were similar, with minimal accumulation at steady state. Maribavir was safe and well tolerated. Taste disturbance was the most frequently reported adverse event. These results will further guide evaluation of the drug interaction potential and clinical development of maribavir.