Holland M J, Simon E J
Neuropeptides. 1984 Dec;5(1-3):65-8. doi: 10.1016/0143-4179(84)90028-3.
Rats were injected i.v. with 3H-etorphine (200 ng/Kg). At least 85% of the dose was cleared from the blood in the first 2 min. Blood levels continued to fall slowly from about 5% of the administered dose after 15 min to less than 2% after 3 hours. Although more than 15% of the dose was found in the liver and kidney after 15 min, labeled material did not further accumulate in these organs, but decreased to about 3% after 3 hours. The concentration of labeled material (dpm/mg tissue) in cerebellum was less than half that attained in other brain regions at early time points, probably reflecting the low number of opiate receptors in this region. After 2 hours, however, there was little difference between cerebellum and other brain regions. The highest brain concentrations observed were at the earliest time point examined (7 min). An open four compartment kinetic model was constructed to fit the data for etorphine concentrations in (i) plasma, (ii) cerebellum, and (iii) brain (excluding cerebellum). The model has 3 spatial compartments: plasma, brain, and all tissues other than brain. Etorphine in brain occupies either of 2 functional compartments: one representing receptor-bound ligand and the other, the sum of free and nonspecifically bound ligand. The dissociation rate constant for etorphine in vivo obtained by fitting model equations to data was 0.06 min-1, similar to that obtained in vitro in the presence of 150 mM sodium ion.
给大鼠静脉注射3H-埃托啡（200纳克/千克）。至少85%的剂量在最初2分钟内从血液中清除。血药浓度在15分钟后从给药剂量的约5%开始持续缓慢下降，3小时后降至2%以下。虽然15分钟后超过15%的剂量在肝脏和肾脏中被发现，但标记物在这些器官中并未进一步蓄积，3小时后降至约3%。小脑中标记物的浓度（每分钟衰变数/毫克组织）在早期时间点不到其他脑区的一半，这可能反映了该区域阿片受体数量较少。然而，2小时后，小脑和其他脑区之间几乎没有差异。观察到的最高脑浓度出现在最早检测的时间点（7分钟）。构建了一个开放的四室动力学模型来拟合埃托啡浓度在（i）血浆、（ii）小脑和（iii）脑（不包括小脑）中的数据。该模型有3个空间室：血浆、脑和脑以外的所有组织。脑中的埃托啡占据2个功能室中的一个：一个代表与受体结合的配体，另一个代表游离和非特异性结合配体的总和。通过将模型方程拟合到数据中获得的埃托啡在体内的解离速率常数为0.06分钟-1，与在150毫摩尔钠离子存在下体外获得的值相似。
