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Antimicrobial Agents and Chemotherapy, April 2006, p. 1130-1135, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1130-1135.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Joseph D. Ma,^1, Anne N. Nafziger,^1,2, Stephen A. Villano,³ Andrea Gaedigk,⁴ and Joseph S. Bertino Jr.^1,2*

Clinical Pharmacology Research Center, The Research Institute,¹ Department of Medicine, Bassett Healthcare, Cooperstown, New York,² ViroPharma Incorporated, Exton, Pennsylvania,³ Division of Clinical Pharmacology and Experimental Therapeutics, Children's Mercy Hospital and Clinics, Kansas City, Missouri⁴

Received 22 July 2005/ Returned for modification 8 September 2005/ Accepted 9 January 2006

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.

Present address: Amgen Inc., Thousand Oaks, CA 91320.

Present address: ORI Drug Development Center, Ordway Research Institute, Inc., Albany, NY 12208.

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