Methods for treating noninfected macaque fetuses with azidothymidine (AZT) in utero were studied in order to determine the potential for toxicity during prenatal life. Multiple routes were investigated including direct fetal treatment [intraamniotic (n = 4) or intraperitoneal (IP) (n = 14) every 10 days, gestational day (GD) 60-160; 20 mg/kg] and maternal treatment [oral 60 mg/kg/day divided every 8 h (n = 4) or via subcutaneous (SQ) osmotic pumps (Alzet®), 1.4 mg/kg/h (n = 4) or 1.1 mg/kg/h (n = 10); GD 60-160]. Ten vehicle controls were included. Prenatal growth was monitored sonographically and fetal (amniotic fluid and blood) and maternal (blood and urine) samples were collected periodically to monitor drug levels and hematologic status. Results indicated an increased incidence of abortion, fetal/neonatal death, and premature delivery in all AZT-treated groups with minimal effects (1 abortion, 1 premature delivery) at 1.1 mg/kg/h SQ. Statistically significant effects on maternal and fetal red cell counts, hemoglobins, and hematocrits were observed with maternal oral and SQ administration but not direct fetal treatment. Drug levels in maternal (pumps: 0.13 ± 0.02 μg/ml; oral: 0.79 ± 0.08) and fetal plasma (pumps: 0.17 ± 0.02 μg/ml; oral: 1.02 ± 0.16) were similar during the course of gestation, with no indication of drug accumulation over time. All neonates were grossly normal at delivery with no significant effects on Apgar scores or overall body size. Chronic treatment via the maternal SQ (pump) route at the lowest dose studied was determined to be the most efficient; continuous and consistent drug levels were achieved in both the fetus and dam throughout gestation, although prenatal hematologic toxicity was observed.
|Original language||English (US)|
|Number of pages||10|
|Journal||Pediatric AIDS and HIV Infection|
|State||Published - 1994|
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health