DISTRIBUTION OF CHLORPROMAZINE AND IMIPRAMINE IN ADIPOSE AND OTHER TISSUES OF RATS
DISTRIBUTION OF CHLORPROMAZINE AND IMIPRAMINE IN ADIPOSE AND OTHER TISSUES OF RATS
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DOI：
10.1016/0024-3205(83)90742-7
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发表时间：
1983-01-01
期刊：
影响因子：
6.1
通讯作者：
MOOR, M
中科院分区：
文献类型：
--
作者：
BICKEL, MH;GRABER, BE;MOOR, M
研究了比硫喷妥更亲油的两种药物氯丙嗪和丙咪嗪在大鼠体内的脂肪组织动力学。单次静脉注射后。随着药物剂量的增加，药物在脂肪和其他各种组织中分布的时间进程被跟踪，直到其在脂肪组织中的浓度下降。在此条件下，两种药物的作用几乎相同。在分析的组织中，除血浆外，脂肪组织中的浓度最低。在大约30分钟后达到最大浓度时，总脂肪组织仅包含所用药物剂量的3%。脂肪/血浆和脂肪/肺浓度比分别为2~5和0.05。口服最大耐受量丙咪嗪3wk后，出现相似的稳态血药浓度比(血浆：脂肪：脑：肺，1：3：12：96)。脂肪组织中丙咪嗪/去甲基米帕明的比值约为1，去甲基米帕明的稳态水平不随时间增加。许多基本的亲脂性药物并不储存在脂肪组织中。氯丙嗪和丙咪嗪现在清楚地表明了这一点，即使在丙咪嗪的极端亚慢性条件下也是如此。
Adipose tissue kinetics of chlorpromazine and imipramine, 2 drugs which are more lipophilic than thiopental, were studied in the rat. After single i.v. doses, the time-course of drug distribution was followed in adipose and various other tissues until their concentrations in adipose tissues declined. Under these conditions the 2 drugs behaved almost identically. Among the tissues analyzed, the lowest concentrations were found in adipose tissue, with the exception of plasma. At its maximum concentration after about 30 min, total adipose tissue contained only 3% of the dose of administered drugs. Adipose/plasma and adipose/lung concentration ratios were 2-5 and 0.05, respectively. After maximum tolerated oral doses of imipramine for 3 wk, similar steady state concentration ratios (plasma:adipose:brain:lung, 1:3:12:96) were observed. In adipose tissue the imipramine/desmethylimipramine ratio was about 1, and the desmethylimipramine steady state levels did not increase with time. Many basic lipophilic drugs are not stored in adipose tissue. This is now clearly shown for chlorpromazine and imipramine, even under extreme, subchronic conditions in the case of imipramine.