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 <10.0 gm/dl) during therapy and 9 (28.1%) had neutropenia (neutrophil count ≤750 cells/mm3); 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 (p<0.0001). Concurrently, there was a significant decrease in serum half-life from 3.12 hours in infants ≤14 days to 1.87 hours in older infants (p=0.0002). Oral absorption was satisfactory and bioavallability decreased significantly with age, from 89% in infants ≤14 days to 61% in those >14 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.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health