changes in the pharmacokinetics of glibenclamide in rats with streptozotocin-induced diabetes mellitus
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ID: 165091
2012
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Abstract
The aim of this study was to investigate the pharmacokinetics of glibenclamide (Gli) administrated orally and intravenously to normal and diabetic rats. The AUC(0–720 min) of orally administered Gli in diabetic rats (321.24 mg min/L) was greater than that (57.752 mg min/L) in normal rats. CL (0.019 L/min/kg) was significantly slower than that (0.092 L/min/kg) of normal rats. The AUC(0–480min) of intravenous Gli in diabetic rats (1528.280 mg min/L) also was significantly greater than that (509.523 mg min/L) in normal rats, and CL was decreased approximately 3-fold. No significant difference in intestinal absorption of Gli was observed between normal and diabetic rats as determined by in situ single-pass intestinal perfusion. The clearance of Diclofenac (a substrate of CYP2C9) was determined to evaluate changes in hepatic drug-metabolizing enzyme activity in rats. The CL in diabetic rats was significantly lower (42.43% decrease) than that in normal rats. Hepatic protein expression of CYP2C9 was measured using Western blot analysis; compared with normal rats, the hepatic protein expression of CYP2A9 was decreased in diabetic rats. Therefore, the slower clearance of Gli in diabetic rats can be attributed primarily to the lower expression of hepatic CYP2C9.
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li2012actachanges
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|---|---|
| Authors | ;Yuqing Li;Yuhui Wei;Fan Zhang;Dan Wang;Xinan Wu |
| Journal | energy policy |
| Year | 2012 |
| DOI |
10.1016/j.apsb.2012.01.005
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