Pharmacokinetics (PK) of ethinylestradiol/levonorgestrel co-administered with atazanavir/cobicistat

Abstract

Background and objectives: Access to safe and reliable contraception in the context of ARVs is essential. This study aimed to investigate the steady-state pharmacokinetics (PK) of ethinylestradiol/levonorgestrel (EE/LNG) 30/150 μg (Microgynon®) and atazanavir/cobicistat (ATV/COBI) 300/150 mg (Evotaz®), co-administered in HIV negative female volunteers, and assess its safety and tolerability. Methods: This phase 1, open label, 57-day, cross over, PK study randomized participants to one of two groups: (i) group 1 received EE/LNG alone on days 1–21, EE/LNG (21 days) + ATV/COBI (14 days) in the co-administration phase (days 22–42) and ATV/COBI alone on days 43–56; (ii) group 2 followed the same sequence but started with ATV/COBI and concluding with EE/LNG. Each group underwent intensive PK sampling on days 14, 35, and 56. EE/LNG and ATV/COBI concentrations were measured using validated LC-MS/MS methods. Results: Of 14 healthy female volunteers screened, 11 attended baseline and six completed all PK phases (five withdrew secondary to side effects). Paired data were available for analysis in six subjects for EE/LNG and eight for ATV/COBI. Geometric mean ratios (GMR, with versus without ATV/COBI) and 90% confidence intervals (CI) for LNG Cmax, AUC0-24, C24 were 0.83 (0.68–1.02), 0.92 (0.71–1.18), 1.01 (0.73–1.38). GMR and 90% CI for EE Cmax, AUC0-24, C24 were 1.05 (0.92–1.19), 1.01 (0.83–1.22), 0.75 (0.60–0.93). No grade 3 or 4 adverse events or laboratory abnormalities were observed in the women who completed the study. Conclusions: Our findings showed no significant changes in LNG concentrations and a 25% decrease in EE C24 when EE/LNG was co-administered with ATV/COBI.

Keywords

• atazanavir
• cobicistat
• oral contraceptive
• levonogestrel
• ethinylestradiol