Pharmacokinetic evaluation of the effects of ribavirin on zidovudine triphosphate formation: ACTG 5092s Study Team.

TitlePharmacokinetic evaluation of the effects of ribavirin on zidovudine triphosphate formation: ACTG 5092s Study Team.
Publication TypeJournal Article
Year of Publication2007
AuthorsAweeka FT, Kang M, Yu J-Y, Lizak P, Alston B, Chung RT
Corporate AuthorsAIDS Clinical Trials Group 5092s Study Team
JournalHIV Med
Volume8
Issue5
Pagination288-94
Date Published2007 Jul
ISSN1464-2662
KeywordsAdult, Antiviral Agents, Area Under Curve, Drug Interactions, Hepacivirus, Hepatitis C, Chronic, HIV Infections, HIV-1, Humans, Middle Aged, Phosphorylation, Reverse Transcriptase Inhibitors, Ribavirin, Zidovudine
Abstract

OBJECTIVES: Ribavirin (RBV) is used for the treatment of hepatitis C virus (HCV) infection in subjects with HIV-1 infection who may require antiretroviral treatment (ART) with nucleoside reverse transcriptase inhibitors including zidovudine (ZDV). We sought to investigate the potential antagonism between RBV and ZDV by evaluating the impact of RBV on the formation of intracellular ZDV triphosphate (TP) in HIV-infected patients receiving ZDV who were treated for HCV infection.

METHODS: Serial plasma and intracellular ZDV TP pharmacokinetics (PK) were determined in 14 subjects at entry (within 2 weeks prior to RBV administration) and at 8 weeks following initiation of RBV. Intracellular ZDV TP in peripheral blood mononuclear cells (PBMC) was quantified by a validated cartridge/liquid chromatography/tandem mass spectrometry method. PK exposure was estimated from the steady-state area under the concentration vs time curve (AUC(0-12 h)) in plasma and PBMC.

RESULTS: Ribavirin did not have a statistically significant impact on ZDV TP AUC(0-12 h), plasma ZDV AUC(0-12 h) or the ratio of ZDV TP AUC(0-12 h) to plasma ZDV AUC(0-12 h), although there was a trend towards an increase post-RBV ratio compared with pre-RBV. There was extensive variability in the ZDV TP AUC(0-12 h).

CONCLUSIONS: Ribavirin did not inhibit formation of ZDV TP in PBMC in 14 patients receiving ZDV as part of ART and RBV-based HCV therapy for 8 weeks. These results are consistent with those of a previously published limited study in seven subjects. These PK findings should be weighed carefully against emerging clinical reports of significant anaemia associated with combination ZDV and high-dose RBV therapy.

DOI10.1111/j.1468-1293.2007.00472.x
Alternate JournalHIV Med.
PubMed ID17561874
Grant ListAI38858 / AI / NIAID NIH HHS / United States