中枢作用药物的脑药代动力学：一项定量放射自显影研究

Brain pharmacokinetics of centrally acting drugs, a quantitative autoradiographic study.

作者信息

Keller F, Waser P G

出版信息

Arch Int Pharmacodyn Ther. 1984 Feb;267(2):200-12.

Abstract

The concentration kinetics of 14C labeled diazepam, chlorpromazine and iodoantipyrine were studied in several regions of rat brain shortly after intravenous (i.v.) administration by a quantitative autoradiographic method. A highly significant linear relationship was found between regional diazepam resp. chlorpromazine concentration, and regional cerebral blood flow (rCBF) 1 min after injection. Moreover, a linear relationship was found between rCBF and, on the other hand, firstly diazepam concentration decrease between 1 and 2 min, secondly increase in chlorpromazine concentration between 1 and 5 min, and finally decrease of chlorpromazine concentration between 5 and 30 min. The regional kinetics of diazepam were compared with those of iodoantipyrine, a tracer assumed to be freely diffusible through the blood-brain barrier.

摘要

采用定量放射自显影法，研究了静脉注射（i.v.）后不久，大鼠脑几个区域中14C标记地西泮、氯丙嗪和碘安替比林的浓度动力学。注射后1分钟，区域地西泮或氯丙嗪浓度与区域脑血流量（rCBF）之间发现高度显著的线性关系。此外，另一方面，还发现rCBF与以下情况存在线性关系：一是1至2分钟内地西泮浓度降低，二是1至5分钟内氯丙嗪浓度升高，最后是5至30分钟内氯丙嗪浓度降低。将地西泮的区域动力学与碘安替比林的区域动力学进行了比较，碘安替比林是一种假定可自由透过血脑屏障的示踪剂。