Ha J C, Nosbisch C, Conrad S H, Ruppenthal G C, Sackett G P, Abkowitz J, Unadkat J D
Regional Primate Research Center, University of Washington, Seattle 98195.
J Acquir Immune Defic Syndr (1988). 1994 Feb;7(2):154-7.
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.
本研究的目的是确定孕期给予猪尾猕猴齐多夫定（AZT）对母体、胎儿和婴儿的毒性。整个孕期通过胃管给怀孕的猕猴服用AZT（每4小时1.5毫克/千克剂量）或水。监测母体的AZT浓度和血液学变化，并通过超声监测胎儿生长。出生时评估婴儿的血细胞比容，并对后代的神经、感知和运动发育进行9至10个月的评估。12次妊娠足月分娩。AZT的平均血浆浓度与人体研究中的浓度相当。怀孕母猴的血红蛋白显著下降并维持在低水平，而血小板在治疗期间增加，但在研究结束前恢复正常。胎儿生长的任何超声测量指标均无显著差异，暴露于AZT的婴儿几乎没有行为延迟或损伤。我们预测，此剂量的产前AZT暴露对人类无显著毒性作用。
