Hartvig P, Lindberg B S, Lilja A, Lundqvist H, Långström B, Rane A
Hospital Pharmacy, University of Uppsala, Sweden.
Dev Pharmacol Ther. 1989;12(2):74-80.
The noninvasive radiotracer technique, positron emission tomography, has been applied in studies on the transfer of drugs from mother to fetus in Rhesus monkeys. 11C-labelled morphine or heroin was administered intravenously to pregnant monkey and the radioactivities with time were measured in the placenta, fetal liver and maternal blood. The information from the 11C-morphine experiment was supplemented with data from the simultaneous administration of 14C-morphine followed by the analysis of unchanged drug and metabolites in maternal blood and also in one sample from fetal blood. In placenta, 11C-morphine and 11C-heroin rapidly reached high radioactivities already within the first few minutes after administration. The transfer of 11C-morphine-derived radioactivity to the fetus was also rapid, although there was a lag-time in relation to the placental uptake. The elimination rate of the radioactivity was fast from the blood, placenta and the fetal liver and in plasma there was a rapid appearance of conjugated morphine metabolites. The fetal plasma concentration of morphine was twice that in maternal plasma 100 min after injection. The transfer of 11C-heroin-derived radioactivity to the fetus was even faster than was the elimination of radioactivity. The plasma kinetics of morphine in the mother and fetus was simulated in a compartment flow model and simulated concentrations agreed well with measured values.
非侵入性放射性示踪技术——正电子发射断层扫描，已应用于恒河猴母体向胎儿药物转运的研究。给怀孕的猴子静脉注射11C标记的吗啡或海洛因，并测量胎盘、胎儿肝脏和母体血液中随时间变化的放射性。11C-吗啡实验的信息通过同时注射14C-吗啡后补充的数据得到补充，随后对母体血液以及一份胎儿血液样本中的未变化药物和代谢物进行分析。在胎盘中，11C-吗啡和11C-海洛因在给药后的最初几分钟内迅速达到高放射性。11C-吗啡衍生的放射性向胎儿的转运也很快，尽管相对于胎盘摄取存在滞后时间。放射性从血液、胎盘和胎儿肝脏中的消除速率很快，并且在血浆中迅速出现结合型吗啡代谢物。注射100分钟后，胎儿血浆中吗啡的浓度是母体血浆中的两倍。11C-海洛因衍生的放射性向胎儿的转运甚至比放射性的消除还要快。在房室流动模型中模拟了母体和胎儿体内吗啡的血浆动力学，模拟浓度与测量值吻合良好。
