Methods: This was an open-label, 2-period, fixed-sequence DDI study in 14 healthy, postmenopausal or oopherectomized females aged 50 to 64. A single dose of LNG 0.15 mg/EE 0.03 mg was given followed by a 7-day washout. MK-8591 20 mg was then dosed once weekly for 3 weeks; a single dose of LNG 0.15 mg/EE 0.03 mg was given concomitantly with the 3rd dose of MK-8591. PK samples were collected for evaluation of LNG and EE levels. Individual values of AUC0-inf and Cmax were natural log-transformed prior to analysis and evaluated separately using a linear mixed effects model with a fixed effects term for treatment. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the treatment measurements within each subject.
Results: The PK of EE and LNG were not meaningfully altered by co-administration with MK-8591. For the comparison of (MK-8591 + LNG/EE) / (LNG/EE alone), the geometric mean ratios (GMRs) (90% confidence intervals (CIs)) for LNG AUC0-inf and Cmax were 1.13 (1.06, 1.20) and 0.965 (0.881, 1.06), respectively. For EE the GMRs (90% CI) for AUC0-inf and Cmax were 1.05 (0.981, 1.11) and 1.02 (0.971, 1.08), respectively. Co-administration of all three drugs was generally well tolerated.
Conclusion: The results of this study support use of hormonal contraceptives in HIV-infected patients receiving MK-8591.
Merck & Co, Inc:
D. Rudd, Merck & Co., INC.: Employee , Salary .
S. Zhang, Merck & Co, Inc: Employee , Salary .
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D. Brimhall, None
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