Zidovudine Pharmacokinetics in HIV‐Positive Women During Different Phases of the Menstrual Cycle

Abstract

Study Objective. To examine the pharmacokinetics of zidovudine during the menstrual cycle in human immunodeficiency virus‐ (HIV‐) positive women.Design. Open, unblinded study.Setting. A women's clinic for acquired immunodeficiency syndrome (AIDS) at a large medical center.Patients. HIV‐positive women with a CD4+ cell count above 200/mm3, receiving long‐term zidovudine therapy, with a history of regular menstrual cycles.Interventions. All patients received a 100‐mg dose of zidovudine in the fasted state on three occasions.Measurements and Main Results. Zidovudine and zidovudine‐glucuronide plasma concentrations were measured with radioimmunoassay to determine the pharmacokinetic characteristics during each menstrual phase. The drug's mean peak plasma concentrations (range 233–808 ng/ml) were 556 ± 145, 385 ± 132, and 495 ± 143 ng/ml during the menstrual, late follicular‐ovulatory, and luteal phases, respectively. Initially, plasma concentrations declined in a linear fashion from 0 to 4 hours, with a prolonged elimination phase in many patients after 4 hours. The mean zidovudine area under the curve was 886 ± 156, 845 ± 268, and 775 ± 167 ng·hour/ml. The mean percentage of dose recovered was 44.2 ± 26.0, 56.9 ± 19.1, and 42.2 ± 16.6, respectively.Conclusions. The pharmacokinetics of zidovudine were not different during the three phases of the menstrual cycle; however, considerable intrapatient and interpatient variability was noted for many of the values.