title: Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS Clinical Trials Group protocol 332.
abstract: 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.
authors.affiliation: Department of Pediatrics, Children's Hospital at Albany Medical Center, Albany, New York 12208, USA. drnancyw@yahoo.com
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wade
authors.forename: Jashvant D
authors.initials: JD
authors.lastname: Unadkat
authors.forename: Sharon
authors.initials: S
authors.lastname: Huang
authors.forename: David E
authors.initials: DE
authors.lastname: Shapiro
authors.forename: Anita
authors.initials: A
authors.lastname: Mathias
authors.forename: Salih
authors.initials: S
authors.lastname: Yasin
authors.forename: Gregory
authors.initials: G
authors.lastname: Ciupak
authors.forename: D Heather
authors.initials: DH
authors.lastname: Watts
authors.forename: Isaac
authors.initials: I
authors.lastname: Delke
authors.forename: Mobeen
authors.initials: M
authors.lastname: Rathore
authors.forename: Jane
authors.initials: J
authors.lastname: Hitti
authors.forename: Lisa
authors.initials: L
authors.lastname: Frenkel
authors.forename: Renee
authors.initials: R
authors.lastname: Samelson
authors.forename: Mary Elizabeth
authors.initials: ME
authors.lastname: Smith
authors.forename: Lynne
authors.initials: L
authors.lastname: Mofenson
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Burchett
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D018119:Stavudine