Chronic administration of nevirapine during pregnancy: Impact of pregnancy on pharmacokinetics

Objectives: To determine the impact of pregnancy on the pharmacokinetics (PK) of nevirapine (NVP) during chronic dosing in HIV-infected women and appropriate NVP dosing in this population. Methods: Twenty-six pregnant women participating in two open-label Pediatric AIDS Clinical Trials Group studies (P1022 and P1026S) were evaluated. Each patient received 200mg NVP every 12h and had PK evaluations during the second or third trimester; these evaluations were repeated postpartum. Paired maternal and cord blood NVP concentrations were collected at delivery in nine patients. Ante- and postpartum comparisons were made using paired t-tests and using a 'bioequivalence' approach to determine confidence interval (CI). Results: The average NVP Area Under the Curve (AUC) was 56 ± 13mcg*h/mL antepartum and 61 ± 15mcg*h/mL postpartum. The typical parameters ± standard error were apparent clearance (CL/F)=3.51 ± 0.18L/h and apparent volume of distribution (Vd/F)=121 ± 19.8L. There were no significant differences between antepartum and postpartum AUC or pre-dose concentrations. The AUC ratio was 0.90 with a 90% CI of the mean equal to 0.80-1.02. The median (± standard deviation) cord blood to maternal NVP concentration ratio was 0.91 ± 0.90. Conclusions: Pregnancy does not alter NVPPK and the standard dose (200 mg every 12h) is appropriate during pregnancy.