title: Chronic administration of nevirapine during pregnancy: impact of pregnancy on pharmacokinetics.
abstract: OBJECTIVE
  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.
authors: San Diego Schools of Medicine and Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92103, USA. ecapparelli@ucsd.edu
authors: E V
authors: EV
authors: Capparelli
authors: F
authors: F
authors: Aweeka
authors: J
authors: J
authors: Hitti
authors: A
authors: A
authors: Stek
authors: C
authors: C
authors: Hu
authors: S K
authors: SK
authors: Burchett
authors: B
authors: B
authors: Best
authors: E
authors: E
authors: Smith
authors: J S
authors: JS
authors: Read
authors: H
authors: H
authors: Watts
authors: S
authors: S
authors: Nachman
authors: E M
authors: EM
authors: Thorpe
authors: S A
authors: SA
authors: Spector
authors: E
authors: E
authors: Jimenez
authors: W T
authors: WT
authors: Shearer
authors: M
authors: M
authors: Foca
authors: M
authors: M
authors: Mirochnick
mesh_terms: D000328:Adult; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics*; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000378:metabolism*; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine