Chronic administration of nevirapine during pregnancy: impact of pregnancy on pharmacokinetics.
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.
Capparelli
E V
EV
San Diego Schools of Medicine and Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92103, USA. ecapparelli@ucsd.edu
Aweeka
F
F
Hitti
J
J
Stek
A
A
Hu
C
C
Burchett
S K
SK
Best
B
B
Smith
E
E
Read
J S
JS
Watts
H
H
Nachman
S
S
Thorpe
E M
EM
Spector
S A
SA
Jimenez
E
E
Shearer
W T
WT
Foca
M
M
Mirochnick
M
M
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*
D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine