Golub M S, Eisele J H, Anderson J H
Dev Pharmacol Ther. 1986;9(1):12-22. doi: 10.1159/000457072.
Maternal-fetal distribution of the opiate agents morphine and alfentanil was studied in 3 near-term sheep and rhesus monkeys. Blood samples were obtained from maternal and fetal arteries for radioimmunoassay after placement of catheters under halothane anesthesia. Fetal-maternal ratios (F/M) of plasma morphine concentrations for sheep increased from 0.04 to 0.47 during the first hour after bolus IV injection of 200 micrograms/kg morphine. However, in monkeys, F/M values were considerably higher, increasing from 0.27 to 1.85. Indeed, values over 1.00, indicating higher drug concentrations in fetal than maternal plasma, were seen in two monkeys at 10 and 60 min time points. For alfentanil, a more lipid soluble but highly protein-bound drug, F/M values of plasma concentrations were similar in the two species ranging from 0.1 to 0.6 after injection of 250 micrograms/kg in sheep and 125 micrograms/kg in monkeys. Quantitation of morphine glucuronide, the principal metabolite of morphine and total morphine-like immunoactivity, suggested that morphine was metabolized more rapidly in monkey dams than in sheep, and that morphine glucuronide was more readily distributed to monkey than sheep fetus. These data suggest that morphine, but not alfentanil, transfers more readily from dam to fetus in near-term monkeys than in sheep.
在3只近足月的绵羊和恒河猴中研究了阿片类药物吗啡和阿芬太尼在母胎间的分布情况。在氟烷麻醉下放置导管后，从母羊和胎儿的动脉采集血样进行放射免疫分析。在静脉推注200微克/千克吗啡后的第一个小时内，绵羊血浆吗啡浓度的胎儿-母体比率（F/M）从0.04增加到0.47。然而，在猴子中，F/M值要高得多，从0.27增加到1.85。事实上，在10分钟和60分钟时间点的两只猴子中观察到F/M值超过1.00，这表明胎儿血浆中的药物浓度高于母体血浆。对于阿芬太尼，一种脂溶性更高但蛋白结合率高的药物，在绵羊注射250微克/千克、猴子注射125微克/千克后，两种动物血浆浓度的F/M值相似，范围在0.1至0.6之间。对吗啡的主要代谢产物吗啡葡糖苷酸和总吗啡样免疫活性的定量分析表明，吗啡在猴母体中的代谢比在绵羊中更快，并且吗啡葡糖苷酸比绵羊胎儿更容易分布到猴胎儿中。这些数据表明，在近足月的猴子中，吗啡比阿芬太尼更容易从母体转移到胎儿体内，而在绵羊中则不然。
