Ha J C, Nosbisch C, Abkowitz J L, Conrad S H, Mottet N K, Ruppenthal G C, Robinette R, Sackett G P, Unadkat J D
Regional Primate Research Center, Department of Psychology, University of Washington, Seattle 98195-7330, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998 May 1;18(1):27-38. doi: 10.1097/00042560-199805010-00005.
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.
在整个妊娠期接触齐多夫定（AZT）的母猴和胎儿中研究了该药物的毒性。14只无病毒的雌性猕猴（猪尾猕猴）被随机分配到AZT组或对照组。AZT组动物通过胃导管每4小时接受1.5mg/kg的药物，其产生的血浆浓度与服用500至600mg/天AZT的人类相似。对照组动物也通过胃导管接受水安慰剂。一些动物参与了两组实验。所有雌性均与同一只雄性交配；41次交配产生了20次怀孕，其中16次足月分娩（AZT组雌性9次；对照组雌性7次）。AZT组动物出现了无症状的大细胞性贫血，但停用AZT后血液学参数恢复正常。孕期总白细胞计数下降，且AZT给药使其进一步受到影响。暴露于AZT的婴儿出生时轻度贫血。AZT导致生长、觅食和寻鼻反射以及视觉上注视和追踪近刺激的能力出现缺陷，但这些缺陷会随着时间消失。这些数据表明，子宫内早期接触AZT对胎儿应无不可逆的不良影响。
