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.
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.
Ma
Joseph D
JD
Clinical Pharmacology Research Center, The Research Institute, Inc., 150 New Scotland Ave., Albany, NY 12208, USA.
Nafziger
Anne N
AN
Villano
Stephen A
SA
Gaedigk
Andrea
A
Bertino
Joseph S
JS
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism; D012263:Ribonucleosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D013810:Therapeutic Equivalency; D014969:Xanthine Oxidase / Q000378:metabolism; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
D000998:Antiviral Agents; D001189:Aryl Hydrocarbon Hydroxylases; D001191:Arylamine N-Acetyltransferase; D001562:Benzimidazoles; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D006899:Mixed Function Oxygenases; D012263:Ribonucleosides; D014969:Xanthine Oxidase; C450260:CYP2C9 protein, human; C045793:CYP2C19 protein, human; C478900:NAT2 protein, human; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole