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Ha James C.; Nosbisch, Connie; Abkowitz, Janis L.; Conrad, Suzanne H.; Mottet, Karle N.; Ruppenthal, Gerald C.; Robinette, Renee; Sackett, Gene P.; Unadkat, Jashvant D.
Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology: May 1st, 1998

The toxicity of azidothymidine (AZT) was studied in monkey dams and fetuses that were exposed to the drug over the entire gestational period. Fourteen virus-free female macaques (Macaca nemestrina) were randomly assigned to AZT or control groups. AZT animals received the drug through a gastric catheter at a dose of 1.5 mg/kg every 4 hours, which produced plasma concentrations similar to those in humans taking 500 to 600 mg/day of AZT. Control animals received water placebo, also through gastric catheter. Some animals participated in both groups. All females were mated with the same male; 41 matings produced 20 pregnancies, of which 16 were carried to term (9 in AZT females; 7 in control females). The AZT animals developed an asymptomatic macrocytic anemia, but hematologic parameters returned to normal when AZT was discontinued. Total leukocyte count decreased during pregnancy and was further affected by AZT administration. AZT-exposed infants were mildly anemic at birth. AZT caused deficits in growth, rooting and snouting reflexes, and the ability to fixate and follow near stimuli visually, but the deficits disappeared over time. These data indicate that early exposure to AZT in utero should have no irreversible adverse effects on the fetus.

Address correspondence and reprint requests to Jashvant Unadkat, Department of Pharmaceutics, Box 357610, University of Washington, Seattle, WA 98195-7330, U.S.A.

Manuscript received May 1, 1997; accepted November 4, 1997.

© Lippincott-Raven Publishers.