脱水对药物药代动力学的影响：药物代谢与肝脏细胞色素P450同工酶之间的相关性

Effects of water deprivation on drug pharmacokinetics: correlation between drug metabolism and hepatic CYP isozymes.

作者信息

Lee Joo Hyun, Oh Jung Mi, Lee Myung Gull

机构信息

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.

出版信息

Arch Pharm Res. 2008 Aug;31(8):951-64. doi: 10.1007/s12272-001-1269-3. Epub 2008 Sep 12.

DOI:10.1007/s12272-001-1269-3

PMID:18787780

Abstract

Male Sprague-Dawley rats deprived of water for 72 h (a rat model of dehydration) showed no change in protein expression of the hepatic microsomal cytochrome P450 (CYP) 1A2, 2B1/2, 2C11, or 3A1/2, but an increase in protein expression (3-fold) and mRNA level (2.6-fold) of CYP2E1. Glucose feeding instead of food normalized CYP2E1 protein expression during dehydration. Here, we review how dehydration can change the pharmacokinetics of drugs reported in the literature via changing CYP isozyme levels. We also discuss how dehydration changes the pharmacokinetics of drugs that are metabolized via renal DHP-I, or are mainly excreted in the urine and bile, and form conjugates.

摘要

雄性Sprague-Dawley大鼠禁食72小时（脱水大鼠模型），其肝微粒体细胞色素P450（CYP）1A2、2B1/2、2C11或3A1/2的蛋白表达未发生变化，但CYP2E1的蛋白表达增加了3倍，mRNA水平增加了2.6倍。脱水期间，喂食葡萄糖而非食物可使CYP2E1蛋白表达恢复正常。在此，我们综述脱水如何通过改变CYP同工酶水平来改变文献中报道的药物的药代动力学。我们还讨论了脱水如何改变通过肾DHP-I代谢、或主要经尿液和胆汁排泄并形成结合物的药物的药代动力学。