Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS Clinical Trials Group protocol 332.
This study evaluates the safety, tolerance, and pharmacokinetics of stavudine (d4T) in human immunodeficiency virus (HIV)-infected zidovudine (ZDV)-intolerant/refusing pregnant women and of single-dose d4T in their infants. Women received d4T and lamivudine (3TC) from enrollment until labor. During labor, women received oral 3TC and either intravenous or oral d4T. Infants received ZDV and 3TC for 6 weeks and a single dose of oral d4T at weeks 1 and 6. Mean maternal antenatal d4T pharmacokinetics (terminal plasma half-life [T1/2], 83.5+/-16.8 min; area under the plasma-concentration time curve [AUC0-infinity), 81.6+/-22.0 microg.min/mL; n=6) were not significantly different from those during labor (T(1/2), 87.3+/-24.7 min; AUC0-infinity, 88.1+/-16.6 microg.min/mL; n=6). Umbilical-cord and maternal plasma concentrations were not significantly different from one another. The oral clearance of d4T in infants was significantly greater at week 6 versus week 1 (6.8+/-1.0 vs. 5.6+/-1.2 mL/min/kg). There were no toxicities, in women or infants, that required discontinuation or modification of the study drug. No infants had positive HIV viral diagnostic tests. d4T with or without 3TC is a potential alternative to ZDV for HIV-infected pregnant women.
Wade
Nancy A
NA
Department of Pediatrics, Children's Hospital at Albany Medical Center, Albany, New York 12208, USA. drnancyw@yahoo.com
Unadkat
Jashvant D
JD
Huang
Sharon
S
Shapiro
David E
DE
Mathias
Anita
A
Yasin
Salih
S
Ciupak
Gregory
G
Watts
D Heather
DH
Delke
Isaac
I
Rathore
Mobeen
M
Hitti
Jane
J
Frenkel
Lisa
L
Samelson
Renee
R
Smith
Mary Elizabeth
ME
Mofenson
Lynne
L
Burchett
Sandra K
SK
D000328:Adult; D000653:Amniotic Fluid; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019259:Lamivudine / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D018119:Stavudine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019562:Viral Load
D019380:Anti-HIV Agents; D019259:Lamivudine; D018119:Stavudine