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

Elliot, Emilie R, Bisdomini, Elisa, Penchala, Sujan Dilly, Khoo, Saye ORCID: 0000-0002-2769-0967, Nwokolo, Nneka and Boffito, Marta (2019) Pharmacokinetics (PK) of ethinylestradiol/levonorgestrel co-administered with atazanavir/cobicistat. HIV research & clinical practice, 20 (3). pp. 1-10.

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Official URL: http://dx.doi.org/10.1080/25787489.2019.1638077

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.

Item Type:	Article
Uncontrolled Keywords:	Atazanavir, cobicistat, oral contraceptive, levonogestrel, ethinylestradiol
Depositing User:	Symplectic Admin
Date Deposited:	01 Aug 2019 15:43
Last Modified:	19 Jan 2023 00:36
DOI:	10.1080/25787489.2019.1638077
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3050766