Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS clinical trials group Protocol 332

Nancy A. Wade, Jashvant D. Unadkat, Sharon Huang, David E. Shapiro, Anita Mathias, Salih Y Yasin, Gregory Ciupak, D. Heather Watts, Isaac Delke, Mobeen Rathore, Jane Hitti, Lisa Frenkel, Renee Samelson, Mary Elizabeth Smith, Lynne Mofenson, Sandra K. Burchett

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 [T 1/2], 83.5 ± 16.8 min; area under the plasma-concentration time curve [AUC 0-∞], 81.6 ± 22.0 μg·min/mL; n = 6) were not significantly different from those during labor (T 1/2, 87.3 ± 24.7 min; AUC 0-∞, 88.1 ± 16.6 μg·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.

Original languageEnglish
Pages (from-to)2167-2174
Number of pages8
JournalJournal of Infectious Diseases
Volume190
Issue number12
DOIs
StatePublished - Dec 15 2004

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Stavudine
Lamivudine
Clinical Protocols
Pregnant Women
Acquired Immunodeficiency Syndrome
Pharmacokinetics
Clinical Trials
HIV
Zidovudine
Pediatrics
Safety
Area Under Curve
Mothers
Umbilical Cord
Routine Diagnostic Tests
Half-Life
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants : Pediatric AIDS clinical trials group Protocol 332. / Wade, Nancy A.; Unadkat, Jashvant D.; Huang, Sharon; Shapiro, David E.; Mathias, Anita; Yasin, Salih Y; Ciupak, Gregory; Watts, D. Heather; Delke, Isaac; Rathore, Mobeen; Hitti, Jane; Frenkel, Lisa; Samelson, Renee; Smith, Mary Elizabeth; Mofenson, Lynne; Burchett, Sandra K.

In: Journal of Infectious Diseases, Vol. 190, No. 12, 15.12.2004, p. 2167-2174.

Research output: Contribution to journalArticle

Wade, NA, Unadkat, JD, Huang, S, Shapiro, DE, Mathias, A, Yasin, SY, Ciupak, G, Watts, DH, Delke, I, Rathore, M, Hitti, J, Frenkel, L, Samelson, R, Smith, ME, Mofenson, L & Burchett, SK 2004, 'Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS clinical trials group Protocol 332', Journal of Infectious Diseases, vol. 190, no. 12, pp. 2167-2174. https://doi.org/10.1086/425903
Wade, Nancy A. ; Unadkat, Jashvant D. ; Huang, Sharon ; Shapiro, David E. ; Mathias, Anita ; Yasin, Salih Y ; Ciupak, Gregory ; Watts, D. Heather ; Delke, Isaac ; Rathore, Mobeen ; Hitti, Jane ; Frenkel, Lisa ; Samelson, Renee ; Smith, Mary Elizabeth ; Mofenson, Lynne ; Burchett, Sandra K. / Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants : Pediatric AIDS clinical trials group Protocol 332. In: Journal of Infectious Diseases. 2004 ; Vol. 190, No. 12. pp. 2167-2174.
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AU - Mathias, Anita

AU - Yasin, Salih Y

AU - Ciupak, Gregory

AU - Watts, D. Heather

AU - Delke, Isaac

AU - Rathore, Mobeen

AU - Hitti, Jane

AU - Frenkel, Lisa

AU - Samelson, Renee

AU - Smith, Mary Elizabeth

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N2 - 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 [T 1/2], 83.5 ± 16.8 min; area under the plasma-concentration time curve [AUC 0-∞], 81.6 ± 22.0 μg·min/mL; n = 6) were not significantly different from those during labor (T 1/2, 87.3 ± 24.7 min; AUC 0-∞, 88.1 ± 16.6 μg·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.

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