Tissue distribution of cocaine in the pregnant rat.
Tissue distribution of cocaine in the pregnant rat.
复制标题
可卡因在怀孕大鼠中的组织分布。
DOI：
10.1016/0024-3205(89)90129-x
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发表时间：
1989
期刊：
影响因子：
6.1
通讯作者：
Braun,SB
中科院分区：
文献类型：
--
作者：
DeVane,CL;Simpkins,JW;Miller,RL;Braun,SB
在妊娠第18或19天，通过单次腹膜内（IP）给予妊娠大鼠盐酸考地平。用高压液相色谱法测定血浆和组织中可卡因和去甲可卡因的浓度。浓度-时间数据的药代动力学分析显示可卡因及其代谢物迅速分布到母体和胎儿组织。与母体血浆相比，胎儿中可卡因浓度-时间曲线下面积（AUC）为3.33。可卡因在母体血浆和胎儿中的半衰期分别为46和55分钟，与人血浆中可卡因消除半衰期的报告值相似。可卡因浓度顺序为胎盘、胎肝、母体心脏、全胎脑、母体脑=母体血浆。去甲可卡因浓度通常低于血浆和组织中可卡因浓度的20%。这些结果支持妊娠啮齿动物给药后胎儿广泛暴露于可卡因。妊娠期可卡因的药效学研究应考虑药物对发育中胎儿的影响。
Cocaine hydrochloride was administered by single intraperitoneal (IP) doses to pregnant rats at day 18 or 19 of gestation. Plasma and tissue cocaine and norcocaine concetrations were measured by high-pressure liquid chromatography. Pharmacokinetic analysis of concentration versus time data showed rapid distribution of cocaine and its metabolite to maternal and fetal tissues. The area under the cocaine concentration versus time curve (AUC) in fetus compared to maternal plasma was 3.33. The half-life of cocaine in the maternal plasma and fetus was 46 and 55 minutes, respectively, similar to values reported for cocaine elimination half-life in human plasma. The order of cocaine concentrations was placenta fetal liver maternal heart whole fetus fetal brain maternal brain = maternal plasma. Norcocaine concentrations were usually less than 20% of cocaine concentrations in plasma and tissues. These results support extensive fetal exposure to cocaine following administration to pregnant rodents. Pharmacodynamic studies of cocaine in pregnancy should consider the effects of the drug on the developing fetus.