Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus

François D. Boucher, John F. Modlin, Stephen Weller, Andrea J Ruff, Mark Mirochnick, Stephen Pelton, Catherine Wilfert, Ross McKinney, Marilyn J. Crain, Mary Maha Elkins, M. Robert Blum, Charles G. Prober

Research output: Contribution to journalArticle

Abstract

This study evaluated the safety, tolerabillity, and pharmacokinetics of zidovudine administered intravenously and orally to infants born to women infected with the human immunodeficiency virus. Thirty-two symptom-free infants were enrolled before 3 months of age. The pharmacokinetics of zidovudine were evaluated in each infant after single intravenously and orally administered doses of zidovudine on consecutive days, and during long-term oral administration of the drug for 4 to 6 weeks. As new patients were enrolled, doses of zidovudine were progressively increased from 2 to 4 mg/kg. Therapy was continued for up to 12 months in 7 of the infants proved to be infected with human immunodeficiency virus. Zidovudine was generally well tolerated; 20 children (62.5%) had anemia (hemoglobin level 3); these hematologic abnormalities usually resolved spontaneously. The total body clearance of zidovudine increased significantly with age, from an average of 10.9 ml/min per kilogram in infants ≤14 days of age to 19.0 ml/min per kilogram in older infants (p14 days of age (p=0.0002). Plasma concentrations of zidovudine were calculated to be in excess of 1 μmol/L(0.267 μg/ml) for 4.12±1.86 hours and 2.25±0.78 hours after oral doses of 2 mg/kg in infants younger than 2 weeks and 3 mg/kg in older infants, respectively. We conclude that zidovudine administered at oral doses of 2 mg/kg every 6 hours to infants aged less than 2 weeks and 3 mg/kg every 6 hours to infants older than 2 weeks resulted in plasma concentrations that are considered virustatic against human immunodeficiency virus. Zidovudine was well tolerated by infants at these doses.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalJournal of Pediatrics
Volume122
Issue number1
DOIs
StatePublished - 1993

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Zidovudine
HIV
Parturition
Pharmacokinetics
Oral Administration
Anemia
Hemoglobins
Safety

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus. / Boucher, François D.; Modlin, John F.; Weller, Stephen; Ruff, Andrea J; Mirochnick, Mark; Pelton, Stephen; Wilfert, Catherine; McKinney, Ross; Crain, Marilyn J.; Elkins, Mary Maha; Blum, M. Robert; Prober, Charles G.

In: Journal of Pediatrics, Vol. 122, No. 1, 1993, p. 137-144.

Research output: Contribution to journalArticle

Boucher, FD, Modlin, JF, Weller, S, Ruff, AJ, Mirochnick, M, Pelton, S, Wilfert, C, McKinney, R, Crain, MJ, Elkins, MM, Blum, MR & Prober, CG 1993, 'Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus', Journal of Pediatrics, vol. 122, no. 1, pp. 137-144. https://doi.org/10.1016/S0022-3476(05)83507-3
Boucher, François D. ; Modlin, John F. ; Weller, Stephen ; Ruff, Andrea J ; Mirochnick, Mark ; Pelton, Stephen ; Wilfert, Catherine ; McKinney, Ross ; Crain, Marilyn J. ; Elkins, Mary Maha ; Blum, M. Robert ; Prober, Charles G. / Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus. In: Journal of Pediatrics. 1993 ; Vol. 122, No. 1. pp. 137-144.
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AU - Wilfert, Catherine

AU - McKinney, Ross

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N2 - This study evaluated the safety, tolerabillity, and pharmacokinetics of zidovudine administered intravenously and orally to infants born to women infected with the human immunodeficiency virus. Thirty-two symptom-free infants were enrolled before 3 months of age. The pharmacokinetics of zidovudine were evaluated in each infant after single intravenously and orally administered doses of zidovudine on consecutive days, and during long-term oral administration of the drug for 4 to 6 weeks. As new patients were enrolled, doses of zidovudine were progressively increased from 2 to 4 mg/kg. Therapy was continued for up to 12 months in 7 of the infants proved to be infected with human immunodeficiency virus. Zidovudine was generally well tolerated; 20 children (62.5%) had anemia (hemoglobin level 3); these hematologic abnormalities usually resolved spontaneously. The total body clearance of zidovudine increased significantly with age, from an average of 10.9 ml/min per kilogram in infants ≤14 days of age to 19.0 ml/min per kilogram in older infants (p14 days of age (p=0.0002). Plasma concentrations of zidovudine were calculated to be in excess of 1 μmol/L(0.267 μg/ml) for 4.12±1.86 hours and 2.25±0.78 hours after oral doses of 2 mg/kg in infants younger than 2 weeks and 3 mg/kg in older infants, respectively. We conclude that zidovudine administered at oral doses of 2 mg/kg every 6 hours to infants aged less than 2 weeks and 3 mg/kg every 6 hours to infants older than 2 weeks resulted in plasma concentrations that are considered virustatic against human immunodeficiency virus. Zidovudine was well tolerated by infants at these doses.

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