Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

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Title Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment
 
Creator Lee, Myung G.
Choi, Young H
Lee, Inchul
 
Description To test the effect of insulin treatment on the pharmacokinetics of metformin in rats with diabetes mellitus induced by alloxan (DMIA rats). The following results were reported from other studies. Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. In DMIA rats, the protein expression and mRNA levels of hepatic CYP2C11 and 3A1/2 decreased and increased, respectively. In rat model of diabetes mellitus induced by streptozotocin, the protein expression of hepatic CYP2D1 was not changed. The increase in hepatic CYP1A2, 2B1, and 2E1, and decrease in hepatic CYP2C11 in DMIA rats was returned to the controls by insulin treatment. METHODS. Metformin (100 mg/kg) was administered intravenously and orally to the control rats, DMIA rats, and DMIA rats with insulin treatment for 3 weeks (DMIA rats with insulin). RESULTS. After intravenous administration of metformin to the DMIA rats, the CLR and CLNR of the drug were significantly slower than the controls. After oral administration of metformin to the DMIA rats, the AUC of the drug was also significantly greater than the controls. After intravenous administration of metformin to the DMIA rats with insulin, the significantly slower CLNR of the drug in the DMIA rats was returned to the controls. The altered pharmacokinetic indices observed following intravenous and oral administration of metformin to DMIA rats returned to the control values in the DMIA rats with insulin. CONCLUSIONS. The significantly slower CLNR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls. The comparable CLNR of metformin between the DMIA rats with insulin and the control rats could be due to restoration of hepatic CYP enzyme changes in DMIA rats to the controls.
 
Publisher Canadian Society for Pharmaceutical Sciences
 
Date 2008-03-26
 
Type info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion

 
Format application/pdf
 
Identifier https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/1608
10.18433/J35P4X
 
Source Journal of Pharmacy & Pharmaceutical Sciences; Vol 11, No 1 (2008); 88-103
Journal of Pharmacy & Pharmaceutical Sciences; Vol 11, No 1 (2008); 88-103
1482-1826
1482-1826
 
Language eng
 
Relation https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/1608/1131
 

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