四氯化碳诱导的大鼠地西泮药代动力学变化可被前列腺素E2的稳定类似物FCE 20700减轻。

Carbon tetrachloride-induced pharmacokinetic changes of diazepam in rats are reduced by a stable analogue of prostaglandin E2 : FCE 20700.

作者信息

Saija A, Padovano I, Puzzolo D, Ceserani R, Costa G

出版信息

Res Commun Chem Pathol Pharmacol. 1985 Nov;50(2):221-32.

Abstract

Rats, given CC14 (6670 mg/Kg, sc), exhibited a significant increase in SGPT (425.7 +/- 51.3 mU/ml), together with impaired pharmacokinetics of intravenous diazepam (t beta 1/2: 53.87 h; AUC: 101.05 micrograms/ml/h) when compared with saline treated animal (SGPT: 33.6 +/- 3.8 mU/ml; t beta 1/2: 2.087 h; AUC: 1.37 micrograms/ml/h). FCE 20700 (5 micrograms/ml, sc) did not change, by itself, either SGPT or diazepam pharmacokinetic parameters, but significantly antagonized the changes induced by CC14 (SGPT: 45.3 +/- 5.3 mU/ml; t beta 1/2: 0.167 h; AUC: 2.426 micrograms/ml/h). Further support to this cytoprotective effects was given by histological examination of the livers. Data indicate that this new prostaglandin E2 derivative might be useful in patients with liver failure.

摘要

给予四氯化碳（6670毫克/千克，皮下注射）的大鼠，其血清谷丙转氨酶（SGPT）显著升高（425.7±51.3毫国际单位/毫升），与盐水处理的动物相比，静脉注射地西泮的药代动力学也受到损害（β半衰期：53.87小时；曲线下面积：101.05微克/毫升/小时）（盐水处理动物的SGPT：33.6±3.8毫国际单位/毫升；β半衰期：2.087小时；曲线下面积：1.37微克/毫升/小时）。FCE 20700（5微克/毫升，皮下注射）本身既不改变SGPT也不改变地西泮的药代动力学参数，但能显著拮抗四氯化碳诱导的变化（SGPT：45.3±5.3毫国际单位/毫升；β半衰期：0.167小时；曲线下面积：2.426微克/毫升/小时）。肝脏组织学检查进一步支持了这种细胞保护作用。数据表明，这种新的前列腺素E2衍生物可能对肝功能衰竭患者有用。