Inhibitory effect of cyclosporine A on the activity of oral hypoglycemic agents in rats
Diabetic patients often have a kidney or pancreas allograft requiring cyclosporine A (CsA) to prevent transplant rejection. These patients usually take p.o. hypoglycemic agents to control their diabetes. Because of the reported adverse effects of CsA on glucose metabolism as well as its potential us...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 258; no. 1; pp. 8 - 12 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Pharmacology and Experimental Therapeutics
01.07.1991
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Subjects | |
Online Access | Get full text |
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Summary: | Diabetic patients often have a kidney or pancreas allograft requiring cyclosporine A (CsA) to prevent transplant rejection.
These patients usually take p.o. hypoglycemic agents to control their diabetes. Because of the reported adverse effects of
CsA on glucose metabolism as well as its potential use in Type II diabetics, we were interested in evaluating the in vivo
effect of CsA on the activity of p.o. hypoglycemic agents. We also wanted to determine if tolbutamide produced any adverse
effects on the pharmacokinetics of CsA. Male, Holtzman rats were administered CsA (p.o.) followed 1 hr later with the hypoglycemic
agent. Two hours later, blood samples were obtained to determine blood glucose levels. Animals treated with CsA alone produced
a significant hyperglycemia. The hypoglycemic effects produced by tolbutamide and glyburide were inhibited in animals treated
concomitantly with CsA. This inhibitory effect was not observed during the first 3 hr of CsA-treatment, could not be overcome
by increasing the dose of the hypoglycemic agent and occurred using small doses. CsA did not, however, interfere with the
activity of exogenous NPH insulin. Tolbutamide was found to have no effect on the acute pharmacokinetics of CsA. The distribution
of CsA was similar to controls in all tissues studied except the liver in which CsA levels were less in tolbutamide-treated
animals. These studies demonstrate that CsA interferes with the effects of p.o. hypoglycemic agents and, therefore, blood
glucose levels should be monitored closely in Type II diabetic patients taking combinations of these drugs. |
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ISSN: | 0022-3565 1521-0103 |