Objective: To examine the pharmacokinetics of zidovudine during each menstrual cycle phase in women with HIV-1 infection.Design: Open-label, nonblinded study.Setting: The immunodeficiency clinic at the Erie County Medical Center, Buffalo, New York.Patients: 12 HIV-seropositive women started and completed the study. Inclusion criteria for subjects included an acceptable medical history, chemistry profile, a complete blood count with differential, lymphocyte profile, urinalysis and history of regular menstrual cycles.Interventions: All patients received a l00mg dose of zidovudine in a fasted state on three occasions.Main Outcome Measures: 8-hour pharmacokinetic profiles in the 12 women were obtained during the menstrual, follicular and luteal phases of the menstrual cycle. Serum estradiol, progesterone, cortisol and CD4+ and CD8+ cell counts were also obtained during each menstrual cycle phase.Results: Considerable intra- and interpatient variability in zidovudine pharmacokinetics was evident. Plasma concentrations declined in a linear fashion over 4 hours following drug administration, with a prolonged elimination phase for most subjects. The overall mean elimination half-life of zidovudine was 1.6+-0.76h (range 0.56 to 3.7h) and the overall mean oral clearance was 2.32+-0.88 L/h/kg (range 1 to 4.7 L/h/kg). Time to maximum plasma drug concentration was 0.58+-0.27h, 0.77+-0.64h and 0.63+-0.29h during the menstrual, follicular and luteal phases, respectively (p = 0.555). The mean peak plasma concentration of zidovudine was 684+-502 mug/L, 666 + 562 (mug/L and 527+- 210mug/L during the three phases, respectively (p = 0.472). The mean zidovudine area under the concentration-time curve (AUC) during the studied phases was 781+-279mug·h/L, 875+-391 mug·h/L and 693+-176 mug·h/L, respectively (p = 0.128). The AUC was negatively correlated with estradiol serum concentration (r = -0.329, p < 0.05).
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