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Antimicrobial Agents and Chemotherapy, May 2008, p. 1794-1798, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.00951-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Effect of Ketoconazole on the Pharmacokinetics of Maribavir in Healthy Adults {triangledown}

D. Ronald Goldwater,1 Carolyn Dougherty,2 Mary Schumacher,2 and Stephen A. Villano2*

PAREXEL International, Baltimore, Maryland,1 ViroPharma Incorporated, Exton, Pennsylvania2

Received 24 July 2007/ Returned for modification 24 September 2007/ Accepted 23 February 2008

Maribavir, an oral antiviral drug with activity against cytomegalovirus, is currently undergoing studies to assess its efficacy and safety as cytomegalovirus prophylaxis following stem cell or solid organ transplantation. The main objective of this study was to assess the effects of oral ketoconazole, a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) isoenzyme, on the pharmacokinetics of maribavir. This was an open-label crossover study with 20 healthy adults. Subjects were administered a single dose of maribavir at 400 mg. After a washout period, subjects received a single dose of ketoconazole at 400 mg followed by a single dose of maribavir. Blood samples were collected for each drug sequence, and pharmacokinetic parameters for maribavir and its principal metabolite, VP 44469, were determined. Safety was evaluated by physical examination, clinical laboratory testing, 12-lead electrocardiogram, and monitoring for adverse events. Ketoconazole moderately reduced the clearance of both maribavir and VP 44469; oral clearance values were 35% and 13% lower, respectively, for maribavir-plus-ketoconazole treatment than for maribavir alone. Based on the assumption of complete inhibition of CYP3A4 activity, CYP3A4 is responsible for 35% of the overall clearance of maribavir. Treatment was generally well tolerated. The most-common adverse event was dysgeusia (taste disturbance), reported by nine (47%) and seven (35%) subjects in the maribavir alone and maribavir-plus-ketoconazole groups, respectively. The pharmacokinetic findings, in combination with the acceptable tolerability within the maribavir and maribavir-plus-ketoconazole treatment groups, suggest that no dose adjustment of maribavir is necessary when coadministered with CYP3A4 inhibitors or substrates.

* Corresponding author. Mailing address: ViroPharma Incorporated, 397 Eagleview Boulevard, Exton, PA 19341. Phone: (610) 458-7300. Fax: (610) 458-7380. E-mail: stephen.villano{at}viropharma.com

{triangledown} Published ahead of print on 3 March 2008.

Antimicrobial Agents and Chemotherapy, May 2008, p. 1794-1798, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.00951-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Trofe, J., Pote, L., Wade, E., Blumberg, E., Bloom, R. D (2008). Maribavir: A Novel Antiviral Agent with Activity Against Cytomegalovirus. The Annals of Pharmacotherapy 42: 1447-1457 [Abstract] [Full Text]  


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