Fetal, infant, and maternal toxicity of zidovudine (azidothymidine) administered throughout pregnancy in Macaca nemestrina.
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.
Ha
J C
JC
Regional Primate Research Center, Department of Psychology, University of Washington, Seattle 98195-7330, USA.
Nosbisch
C
C
Abkowitz
J L
JL
Conrad
S H
SH
Mottet
N K
NK
Ruppenthal
G C
GC
Robinette
R
R
Sackett
G P
GP
Unadkat
J D
JD
D000740:Anemia / Q000139:chemically induced; D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000254:growth & development*; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D019540:Area Under Curve; D001853:Bone Marrow / Q000187:drug effects; D004909:Erythrocyte Indices / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005327:Fetal Resorption / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects*; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D008254:Macaca nemestrina; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D010976:Platelet Count / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
D019380:Anti-HIV Agents; D006454:Hemoglobins; D004921:Erythropoietin; D015215:Zidovudine