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 200 mg NVP every 12 h 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 +/- 13 mcg(*)h/mL antepartum and 61 +/- 15 mcg(*)h/mL postpartum. The typical parameters +/- standard error were apparent clearance (CL/F)=3.51 +/- 0.18 L/h and apparent volume of distribution (Vd/F)=121 +/- 19.8 L. 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 NVP PK and the standard dose (200 mg every 12 h) is appropriate during pregnancy.