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蛋白质缺乏和吐温60对雄性斯普拉格-道利大鼠中丁基羟基茴香醚及其代谢产物药代动力学的影响。

Effect of protein deficiency and Tween 60 on the pharmacokinetics of butylated hydroxyanisole and metabolites in male Sprague-Dawley rats.

作者信息

Kangsadalampai K, Sharma R P, Taylor M J, Salunkhe D K

出版信息

Drug Nutr Interact. 1986;4(3):289-97.

PMID:3956389
Abstract

Radioactive 3H-butylated hydroxyanisole (BHA) at dosages of 250 or 2,500 mg/kg body weight was administered to rats either orally (po) or intraperitonealy (ip) with or without 500 mg Tween 60/kg. The pharmacokinetics of 3H-BHA were evaluated in both control and protein-deficient animals. Blood or urine and feces were collected and analyzed for 3H-BHA equivalents. Using the Autoan/Nonlin69 computer program, most pharmacokinetic profiles of BHA (250 mg/kg) were fit to one-compartment open models with first-order absorption. The exception was the model for ip administration, which resulted in a two-compartment open model with first-order absorption. Increasing the dose of BHA to 2,500 mg/kg altered pharmacokinetics of BHA; no decline in blood levels was observed 48 hours post-injection. Protein deficiency and Tween 60 in combination increased the rate of absorption of BHA. Excretion of 3H-BHA and/or its metabolites in urine and feces was complete 6.5 days after administration of 2,500 mg/kg 3H-BHA.

摘要

将剂量为250或2500毫克/千克体重的放射性3H-叔丁基对苯二酚(BHA)经口(po)或腹腔内(ip)给予大鼠,给药时伴有或不伴有500毫克吐温60/千克。在对照动物和蛋白质缺乏的动物中评估了3H-BHA的药代动力学。采集血液、尿液和粪便,并分析其中3H-BHA当量。使用Autoan/Nonlin69计算机程序,BHA(250毫克/千克)的大多数药代动力学曲线符合具有一级吸收的单室开放模型。腹腔注射给药的模型除外,该模型为具有一级吸收的双室开放模型。将BHA剂量增加到2500毫克/千克会改变BHA的药代动力学;注射后48小时未观察到血药浓度下降。蛋白质缺乏和吐温60共同作用会提高BHA的吸收速率。给予2500毫克/千克3H-BHA后6.5天,尿液和粪便中3H-BHA和/或其代谢产物的排泄完成。

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