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.
Subject(s)
Antiviral Agents/adverse effects , Antiviral Agents/pharmacokinetics , Pyrrolidinones/adverse effects , Pyrrolidinones/pharmacokinetics , Ribavirin/adverse effects , Ribavirin/pharmacokinetics , Adolescent , Adult , Antiviral Agents/administration & dosage , Drug Therapy, Combination , Female , Healthy Volunteers , Humans , Male , Middle Aged , Pyrrolidinones/administration & dosage , Raltegravir Potassium , Ribavirin/administration & dosage , Young AdultABSTRACT
The frequency of spontaneous genital arousal (GA) and persistent genital arousal disorder (PGAD) in women is unknown. The aim of this study was to conduct an anonymous survey to assess the frequency and nature of spontaneous GA and PGAD in women attending a walk-in sexual health clinic in London. Female patients completed a questionnaire, which included demographic information, medical, psychiatric and gynaecology history, the hospital anxiety and depression scale, and a somatization scale. Patients were then asked to complete three questions regarding spontaneous and persistent GA. Any patient with one or more symptoms then answered questions about the distress, intensity and duration of sensations. Ninety-six subjects participated. The mean age was 28.97 years. Thirty-two women (33.3%) answered 'yes' to at least one question regarding spontaneous or persistent GA and six women (6.3%) women answered 'yes' to all three questions. Only one subject fulfilled all five diagnostic criteria for PGAD. In conclusion, women report a high rate of spontaneous GA in the absence of desire or excitement. This has not been well described previously. A small proportion of women report multiple features of spontaneous and persistent GA, with chronicity over years, but without distress in most cases. Larger studies are needed.
