Pharmacokinetic and safety profile of raltegravir and ribavirin, when dosed separately and together, in healthy volunteers

Abstract

Background: Treatment of chronic hepatitis C virus (HCV) infection in HIV-1-co-infected individuals remains challenging due to numerous factors, including drug-drug interactions. The aim of this study was to assess the safety and pharmacokinetic (PK) profile of raltegravir and ribavirin when dosed separately and together.

Methods: Fourteen healthy volunteers [mean (standard deviation) age 35 (10) years, 71% male] entered this phase 1 PK study and received single-dose ribavirin (800 mg) on day 1 (phase 1). Following a washout period, subjects received raltegravir (400 mg twice daily) on days 15-19 (phase 2) and single-dose ribavirin (800 mg) with raltegravir (400 mg) on day 20 (phase 3). Intensive PK sampling was undertaken on days 1, 19 and 20 and differences in geometric mean ratios (GMRs) for PK parameters between study periods were assessed.

Results: No statistically significant differences in PK parameters were observed for raltegravir between phases 2 and 3. A statistically significant decrease in maximum plasma concentration (C(max)) and an increase in time to maximum plasma concentration (T(max)) were observed for ribavirin in phase 3 compared with phase 1 [GMR (95% confidence interval) 0.79 (0.62-1.00) and 1.39 (1.08-1.78), respectively], whereas no significant differences in other ribavirin PK parameters were observed between study phases. No clinically significant safety concerns were reported.

Conclusions: The PK profile of ribavirin is altered when administered with raltegravir (reduced C(max) and increased T(max)), with no safety concerns identified. This is unlikely to be of clinical significance or have an impact on the antiviral effects of ribavirin in HIV-1- and HCV-co-infected subjects.