Indinavir pharmacokinetics during different phases of the menstrual cycle in HIV-infected women

Objective: To characterise the pharmacokinetics of indinavir during different phases of the menstrual cycle in HIV-infected women. Design: Open-label study. Setting: The immunodeficiency clinic at Erie County Medical Center, Buffalo, New York. Patients: Ten HIV-infected women were enrolled in the study. Eligibility criteria included an acceptable medical history, chemistry profile, complete blood count with differential, lymphocyte profile, urinalysis and history of a regular menstrual cycle. Patients had to be on a stable antiretroviral regimen that included indinavir 800mg taken every 8 hours. Interventions: Blood sampling over an 8-hour period following an 800mg dose of indinavir during the menstrual, follicular and luteal phases of the menstrual cycle. Main outcome measures: Pharmacokinetic parameters in ten HIV-infected women adherent with indinavir 800mg every 8 hours during the menstrual, follicular and luteal phases of the menstrual cycle. Serum estradiol and progesterone levels were also obtained during each menstrual cycle phase. Results: The peak plasma concentration, plasma concentration 8 hours after administration of a given dose of indinavir, elimination half-life and oral clearance of indinavir were not significantly different across the menstrual cycle phases. Indinavir exposure varied among the female patients with some individuals having similar areas under the concentration-time curve (AUCs) during the three phases while others had notable differences in AUC. Maximum plasma indinavir concentrations were highest during the follicular phase in four subjects, highest during the luteal phase in two individuals, and highest during the menstrual phase in three patients. Conclusions: No differences were found in indinavir pharmacokinetics during the menstrual cycle phases. Significant intra- and interpatient variability in indinavir pharmacokinetics were observed; however, indinavir exposure in women did not appear to be excessive compared with pharmacokinetic data obtained from prior studies conducted in men.