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Effects of water deprivation on the pharmacokinetics of metformin in rats
Author(s) -
Choi Young H.,
Lee Inchul,
Lee Myung G.
Publication year - 2007
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.564
Subject(s) - metformin , pharmacokinetics , dehydration , endocrinology , medicine , urine , oral administration , excretion , chemistry , pharmacology , diabetes mellitus , biochemistry
It was reported that metformin was mainly metabolized via hepatic CYP2C11, 2D1 and 3A1/2 in rats, and in a rat model of dehydration, the expressions of hepatic CYP2C11 and 3A1/2 were not changed. Hence, it could be expected that the Cl nr of metformin is comparable between two groups of rats if the contribution of CYP2D1 in the rat model of dehydration is not considerable. It was also reported that the timed‐interval renal clearance of metformin was dependent on the urine flow rate in rats. In the rat model of dehydration, the 24h urine output was significantly smaller than in the controls. Hence, the urinary excretion of metformin was expected to be smaller than the controls. The above expectations were proven as follows. After intravenous administration of metformin (100mg/kg) to the rat model of dehydration, the Cl nr were comparable between the two groups of rats. After both intravenous and oral administration of metformin (both 100mg/kg) to the rat model of dehydration, the 24h urinary excretion of the drug was significantly smaller than in the controls. After oral administration of metformin to the rat model of dehydration, the AUC was significantly greater (99.2% increase) than the controls. Copyright © 2007 John Wiley & Sons, Ltd.