Stark R I, Garland M, Daniel S S, Leung K, Myers M M, Tropper P J
Department of Pediatrics, Columbia College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Soc Gynecol Investig. 1997 Jul-Aug;4(4):183-90.
To evaluate the effects of intravenous of zidovudine (AZT) at a dose and duration of infusion comparable to that used clinically on parameters reflective of fetal well-being.
Thirteen chronically instrumented noninfected baboons were monitored during intravenous infusions of AZT. Fetal cardiorespiratory activity and neurobehavioral function were assessed with 4-48-hour infusion of AZT to ten mothers (0.5-2.1 mg/kg per hour) and three fetuses (2-6 mg/h), which resulted in fetal plasma concentration of AZT of 194-3100 ng/ml.
No significant differences were found in the mean values in control periods, before and after infusion with values during infusion for parameters of fetal heart rate and rate variability (n = 7), breathing activity (n = 8), electroencephalographic activity (n = 8), and behavioral state (N = 7). No correlations were found with drug level.
The absence of associations between exposure of the fetal baboon to AZT and changes in parameters reflective of fetal condition suggests that comparable exposure of the human fetus during intravenous infusion of drug would not confound clinical monitoring used to assess fetal well-being. These findings supplement conclusions from clinical research in support of U.S. Public Health Service recommendations that intrapartum fetal monitoring be performed as clinically indicated, not specifically because pregnant patients are treated with intravenous AZT.
评估静脉注射齐多夫定(AZT),其剂量和输注持续时间与临床使用的相当,对反映胎儿健康状况参数的影响。
在对13只长期植入仪器的未感染狒狒静脉输注AZT期间进行监测。对10只母狒狒(每小时0.5 - 2.1毫克/千克)和3只胎儿(每小时2 - 6毫克)进行4 - 48小时的AZT输注,评估胎儿心肺活动和神经行为功能,这导致胎儿血浆中AZT浓度为194 - 3100纳克/毫升。
在胎儿心率和心率变异性(n = 7)、呼吸活动(n = 8)、脑电图活动(n = 8)和行为状态(N = 7)的参数方面,对照期的平均值、输注前和输注后的平均值与输注期间的值相比,未发现显著差异。未发现与药物水平相关。
胎儿狒狒接触AZT与反映胎儿状况的参数变化之间不存在关联,这表明在静脉输注药物期间人类胎儿的类似接触不会混淆用于评估胎儿健康的临床监测。这些发现补充了临床研究的结论,以支持美国公共卫生服务局的建议,即应根据临床指征进行产时胎儿监测,而不是因为孕妇接受静脉注射AZT治疗。