This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liu, P.
Right arrow Articles by Sharma, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, P.
Right arrow Articles by Sharma, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2007, p. 3617-3626, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00526-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Steady-State Pharmacokinetic and Safety Profiles of Voriconazole and Ritonavir in Healthy Male Subjects{triangledown}

Ping Liu,1 Grover Foster,3 Kuan Gandelman,3 Robert R. LaBadie,2 Mark J. Allison,4 Maria J. Gutierrez,5 and Amarnath Sharma1*

Department of Clinical Pharmacology,1 Department of Biostatistics, Pfizer Global Research and Development, New London, Connecticut,2 Department of Clinical Pharmacology, Pfizer Inc., New York, New York,3 MDS Pharma Services, Phoenix, Arizona,4 Comprehensive NeuroScience Inc., Ft. Lauderdale, Florida5

Received 20 April 2007/ Returned for modification 30 June 2007/ Accepted 15 July 2007

Since there is a likelihood of coadministration of voriconazole and ritonavir, two studies were conducted to evaluate the potential of drug interaction. Study A was a randomized, placebo-controlled, two-period, parallel-group trial (n = 34). Study B had the same design without the placebo group (n = 17). In period 1, subjects received 200 mg voriconazole or placebo twice daily (BID) for 3 days (400 mg BID on day 1). In period 2, following a 7-day washout, subjects received ritonavir alone at 400 mg BID (study A) or 100 mg BID (study B) for 10 days (days 11 to 20), and then ritonavir was coadministered with 200 mg BID voriconazole or placebo for the next 10 days (days 21 to 30). Serial plasma samples were collected on days 3, 20, and 30, and safety data were collected throughout the study. High-dose (400 mg BID) ritonavir substantially reduced the steady-state mean voriconazole exposure (area under the concentration-time curve from 0 to 12 h [AUC0-12], –82%; maximum concentration [Cmax], –66%). However, the effect of low-dose (100 mg BID) ritonavir was less pronounced (AUC0-12, –39%; Cmax, –24%). The decrease in voriconazole exposure was probably due to the induction of CYP2C19 and CYP2C9 by ritonavir. It is interesting that one subject in each study exhibited the opposite effect of ritonavir on voriconazole exposure (a 2.5- to 3-fold increase), probably due to lack of CYP2C19. Voriconazole had no apparent effect on the exposure of high-dose ritonavir but slightly decreased the exposure of low-dose ritonavir (AUC0-12, –14%; Cmax, –24%). The safety profile of combination therapy was not notably different from that of voriconazole or ritonavir alone. Due to the significant effect of ritonavir on voriconazole exposure, coadministration of voriconazole with 400 mg BID ritonavir is contraindicated; coadministration with 100 mg BID ritonavir should be avoided, unless an assessment of the benefit/risk to the patient justifies the use.

* Corresponding author. Mailing address: Department of Clinical Pharmacology, Pfizer Global Research and Development, 50 Pequot Avenue, MS6025-A3237, New London, CT 06320. Phone: (860) 732-3217. Fax: (860) 686-5023. E-mail: amarnath.sharma{at}pfizer.com

{triangledown} Published ahead of print on 23 July 2007.

Antimicrobial Agents and Chemotherapy, October 2007, p. 3617-3626, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00526-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yakiwchuk, E. M, Foisy, M. M, Hughes, C. A (2008). Complexity of Interactions Between Voriconazole and Antiretroviral Agents. The Annals of Pharmacotherapy 42: 698-703 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»