Slower clearance of intravenous metformin in rats with acute renal failure induced by uranyl nitrate: Contribution of slower renal and non-renal clearances

被引:9
|
作者
Choi, Young H. [1 ,2 ]
Lee, Inchul [3 ]
Lee, Myung G. [1 ,2 ]
机构
[1] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea
[2] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea
[3] Univ Ulsan, Asan Fdn, Asan Med Ctr, Dept Diagnost Pathol,Coll Med, Seoul 138736, South Korea
关键词
Metformin; U-ARF; Pharmacokinetics; Hepatic CYP2C11 and 2D subfamily; Rats; DIABETES-MELLITUS; PHARMACOKINETICS; METABOLISM;
D O I
10.1016/j.ejps.2009.05.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. It has also been reported that the protein expression and/or mRNA levels of hepatic CYP2C11, 2D subfamily, and 3A1 have decreased, decreased, and increased, respectively, in U-ARF rats. Thus, pharmacokinetic changes of intravenous metformin in U-ARF rats were evaluated. Merformin was administered intravenously at a dose of 50 mg/kg to control and U-ARF rats. After i.v.. administration of metformin to U-ARF rats, its time-averaged total body clearance was significantly slower (95.2% decrease) than controls. This could have been Clue to both significantly slower time-averaged renal clearance (99.1% decrease; due to a urine flow rate-dependent timed-interval renal clearance of the drug, a decrease in renal OCT2, and/or an impaired kidney function in U-ARF rats) and time-averaged non-renal clearance (83.8% decrease; due to a decrease in hepatic CYP2C11 and 2D subfamily in U-ARF rats). (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 7
页数:7
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