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Pharmacokinetics of Nevirapine (NVP) in Pregnant Women and in Their Infants Following In Utero Exposure M. MIROCHNICK*1, S. SIMINSKI2, T. FENTON2, J. SULLIVAN3, and the PACTG 250 Protocol Team. 1Boston Univ. Sch. of Med., Boston, MA; 2Frontier Sci. and Technology Res. Fndn., Amherst, NY, and Brookline, MA; 3Univ. of Massachusetts Med. Ctr., Worcester Background: Administration of a single maternal 200 mg oral NVP dose during labor and a single oral 2 mg/kg NVP dose to the infant at 48-72 hours of life maintains serum NVP conc above 100 ng/ml (10x the in vitro IC50) throughout the first week of life in infants born to mothers with no previous exposure to NVP.(JID 1998;178:368-74.) With chronic therapy NVP induces activity of its own elimination pathway, accelerating clearance. No previous data are available describing NVP pk in mothers during pregnancy and in infants with prolonged in utero NVP exposure before birth. Methods: Pregnant women received daily 200 mg NVP doses starting at 38 wks gest; pk sampling was performed after the 1st dose. NVP dosing continued through labor; infants received 2 mg/kg NVP at 48-72 hours of life. Infant samples for NVP conc were obtained from cord blood, before the NVP dose, 24 hrs after the dose and on day 7. Serum NVP conc were determined by HPLC. The data were compared to those from previous cohorts with initiation of maternal dosing during labor. Results: 11 women were enrolled; 1 infant died in utero prior to the start of maternal NVP dosing. Maternal pk profiles after initial doses at 38 wks gest were similar to those from non-pregnant women, but t1/2 was decreased compared to women dosed during labor (45.6 +/- 12.4 hrs vs 72.5 +/- 36.2 hrs, p=0.037). Compared to infants whose mothers began NVP in labor, the infants whose mothers began NVP during pregnancy had increased median cord blood NVP conc (2396 vs 1147ng/ml) and pre-dose conc (928 vs 475), but NVP conc fell below 100 ng/ml before age 7 days in 4 of 10 infants. Conclusion: NVP pk in pregnant women are similar to those in non-pregnant women. However, when maternal NVP began during pregnancy, a single infant NVP dose at 48-72 hours after birth did not maintain NVP conc above 100 ng/ml through age 7 days in 4 of 10 infants, presumably due to in utero induction of NVP elimination enzymes. Infants born to mothers receiving sustained NVP therapy prior to labor must be dosed more frequently to maintain therapeutic NVP conc throughout the first week of life. Key Words: Pregnancy, Nevirapine, Pharmacology |
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