Pharmacokinetic and safety profile of raltegravir and ribavirin, when dosed separately and together, in healthy volunteers
| Autor: | Rosy Weston, K. Legg, H. Lamba, Myra McClure, Ngaire Latch, Lucy Garvey, Otto Erlwein, J. Ashby, Antonio D'Avolio, Laura Dickinson, Alan Winston, David Back |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Microbiology (medical)
Adult Male Adolescent Hepatitis C virus Integrase inhibitor Pharmacology medicine.disease_cause Antiviral Agents Raltegravir Potassium chemistry.chemical_compound Young Adult Pharmacokinetics Drug Therapy Ribavirin medicine Humans Pharmacology (medical) Adolescent Adult Antiviral Agents administration /&/ dosage/adverse effects/pharmacokinetics Drug Therapy Combination Female Human Experimentation Humans Male Middle Aged Pyrrolidinones administration /&/ dosage/adverse effects/pharmacokinetics Ribavirin administration /&/ dosage/adverse effects/pharmacokinetics Young Adult administration /&/ dosage/adverse effects/pharmacokinetics business.industry Middle Aged Raltegravir Healthy Volunteers Confidence interval Pyrrolidinones Infectious Diseases Human Experimentation chemistry Toxicity Immunology Combination Drug Therapy Combination Female business medicine.drug |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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