Impact of pregnancy on abacavir pharmacokinetics.
OBJECTIVE
To describe abacavir pharmacokinetics during pregnancy and postpartum; physiological changes during pregnancy are known to affect antiretroviral drug disposition.


METHODS
The Pediatric AIDS Clinical Trials Group P1026s study is an on-going, prospective, non-blinded pharmacokinetic study of pregnant women receiving one or more antiretroviral drugs for routine clinical care, including a cohort receiving abacavir 300 mg twice daily.


METHODS
Serial plasma samples (predose, 1, 2, 4, and 6 h postdose) obtained antepartum (30-36 weeks of gestation) and again postpartum (6-12 weeks after delivery) were assayed for abacavir concentration by reversed-phase high-performance liquid chromatography.


RESULTS
Antepartum evaluations were available for 25 women [mean age, 28.6 years (SD, 6); mean third-trimester weight 92 kg (SD, 35.4); and race/ethnicity 52% black, 28% Hispanic, 16% white, 4% Asian], with geometric mean abacavir area under the concentration-time curve (AUC) of 5.9 mg.h/l [90% confidence interval (CI), 5.2-6.8] and maximum plasma concentration (Cmax) of 1.9 mg/l (90% CI, 1.6-2.2). Seventeen women completed postpartum sampling, and the ratios of antepartum to postpartum AUC and Cmax were 1.04 (90% CI, 0.91-1.18) and 0.79 (90% CI, 0.65-0.98), respectively.


CONCLUSIONS
Abacavir AUC during pregnancy was similar to that at 6-12 weeks postpartum and to that for non-pregnant historical controls (5.8 mg.h/l). Consequently, pregnancy does not appear to affect overall abacavir exposure significantly or to necessitate dose adjustments.
Best
Brookie M
BM
University of California San Diego, California 92103-8214, USA. brookie@ucsd.edu
Mirochnick
Mark
M
Capparelli
Edmund V
EV
Stek
Alice
A
Burchett
Sandra K
SK
Holland
Diane T
DT
Read
Jennifer S
JS
Smith
Elizabeth
E
Hu
Chengcheng
C
Spector
Stephen A
SA
Connor
James D
JD
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011446:Prospective Studies; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D000099227:Abacavir