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阿福唑嗪与氯沙坦(细胞色素CYP2C9底物)药代动力学相互作用的体内研究

[In vivo study of the pharmacokinetic interaction of afobazole and losartan (cytochrome CYP2C9 substrate)].

作者信息

Gribakina O G, Kolyvanov G B, Litvin A A, Zherdev V P, Seredin S B

出版信息

Eksp Klin Farmakol. 2013;76(3):35-7.

Abstract

The influence of afobazole on isoenzyme CYP2C9 production in rats was studied using losartan as the marker drug. Single dose of losartan was administered orally without afobazole in a dose of 30 mg/kg and in the same single (30 mg/kg) on the background of 3- and 4-day administration of afobazole in a dose of 5, 25, 75, 100, and 125 mg/kg. At 5 mg/kg (effective dose for anxiolytic effect), afobazole did not cause any induction/inhibition effect on CYP2C9 isoenzyme. A multiple increase in afobazole dose was manifested by a moderate induction effect. The maximum induction effect of afobazole was achieved in a dose of 75 mg/kg. At doses above 75 mg/kg, the induction effect of afobazole was less pronounced.

摘要

以氯沙坦作为标记药物,研究了阿福唑对大鼠同工酶CYP2C9生成的影响。单剂量口服30mg/kg氯沙坦,未使用阿福唑;以及在分别以5、25、75、100和125mg/kg的剂量给予阿福唑3天和4天后,以相同单剂量(30mg/kg)口服氯沙坦。在5mg/kg(抗焦虑作用的有效剂量)时,阿福唑对CYP2C9同工酶未产生任何诱导/抑制作用。阿福唑剂量的成倍增加表现为中度诱导作用。阿福唑在75mg/kg剂量时达到最大诱导作用。在高于75mg/kg的剂量下,阿福唑的诱导作用不太明显。

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