Fetal toxicity of zidovudine (azidothymidine) in Macaca nemestrina: preliminary observations.
The objective of this study was to determine the dam, fetal, and infant toxicity of zidovudine (AZT) administered to pigtailed macaques during pregnancy. Pregnant macaques were administered AZT (1.5 mg/kg/dose every 4 h) or water via gastric catheter throughout pregnancy. AZT concentration and hematological changes were monitored in the dam, and fetal growth was monitored via ultrasound. Infant hematocrit was assessed at birth, and the neurological, perceptual, and motor development of the offspring were assessed for 9 to 10 months. Twelve pregnancies were brought to term. Mean plasma concentrations of AZT were comparable to those in human studies. Hemoglobin dropped significantly in pregnant dams and remained low, whereas platelets increased during treatment but returned to normal before the end of the study. There were no significant differences in any ultrasound measure of fetal growth, and AZT-exposed infants exhibited little behavioral delay or impairment. We predict no significant toxic effects of prenatal AZT exposure at this dosage in humans.
Ha
J C
JC
Regional Primate Research Center, University of Washington, Seattle 98195.
Nosbisch
C
C
Conrad
S H
SH
Ruppenthal
G C
GC
Sackett
G P
GP
Abkowitz
J
J
Unadkat
J D
JD
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D008254:Macaca nemestrina; D011247:Pregnancy; D016216:Ultrasonography, Prenatal; D015430:Weight Gain / Q000187:drug effects; D015215:Zidovudine / Q000493:pharmacokinetics / Q000633:toxicity*
D006454:Hemoglobins; D015215:Zidovudine