Background:  Nevirapine (NVP) in combination with 2 nucleoside analogues is used widely to manage HIV infection and is commonly prescribed during pregnancy to suppress viral replication. The pharmacokinetics of continuous NVP in pregnancy have not been studied. Our objective was to examine the pharmacokinetics of NVP at steady state during 2^nd and 3^rd trimester pregnancy, compared both to historical data and to postpartum pharmacokinetics.

Methods:  We conducted intensive NVP pharmacokinetics analysis in 12 HIV-infected pregnant women on ZDV/3TC/NVP as part of PACTG 1022, a prospective, open-label, randomized clinical trial comparing the efficacy and safety of nelfinavir and NVP-based regimens for antiretroviral-naïve pregnant women. Subjects received NVP 200 mg once daily x 14 days and then 200 mg twice daily. Pharmacokinetics analysis occurred after >4 weeks of treatment, in either second (20±4 weeks gestation, n = 7) or third (34±2 weeks, n = 5) trimester pregnancy. As of October 1, 2003, 9 women have repeated pharmacokinetics evaluation at 8 (±4) weeks postpartum and 3 women are still pregnant. Pharmacokinetic sampling was carried out under steady-state conditions from 0 to 8 hours following an observed dose with the 0 time value representing both 0 and 12 hour exposure. Non-compartmental pharmacokinetics analysis was used to estimate the area under the concentration time curve (AUC, mg*h/mL). Paired t-tests were used to compare Pharmacokinetics AUC and peak concentration (C_max, mg/mL) results during pregnancy and postpartum, with each subject as her own control. Boehringer Ingelheim Pharmaceuticals provided historical mean results based on pharmacokinetic assessments in 35 men and 8 women. 

Results:  The table below summarizes the data currently available for the mean AUC and Cmax values for second and third trimester and postpartum. The second and third trimester AUC and Cmax were similar to each other and to historical mean values of 60.6 mg*h/mL and 6 mg/mL. Among the 9 subjects with paired pregnancy-postpartum data, there was no significant difference in AUC or Cmax between either second and third trimester and postpartum.

Conclusions:  NVP pharmacokinetics appears to be similar in pregnancy compared to historical data for non-pregnant females and males. In addition, there is no significant difference in NVP AUC or C_max between pregnancy and postpartum. These preliminary data imply that the currently recommended NVP dose for non-pregnant adults is also appropriate for pregnant women.

Keywords: nevirapine pharmacology; pregnancy; women's health