Slower clearance of intravenous metformin in rats with acute renal failure induced by uranyl nitrate: contribution of slower renal and non-renal clearances.
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. Metformin was administered intravenously at a dose of 50mg/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 due 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).
Choi
Young H
YH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Lee
Inchul
I
Lee
Myung G
MG
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008687:Metformin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014502:Uranyl Nitrate
D014502:Uranyl Nitrate; D008687:Metformin