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The demethylation of aminopyrine was decreased while the demethylation of p-chloro-N-methylaniline was increased in both alloxan and streptozotocin diabetic isolated perfused male rat livers. Since similar effects of diabetes were observed with traditional microsomal preparations, these observations indicate that the effects of diabetes on drug metabolism observed in isolated microsomal preparations from male rat are an accurate reflection of conditions in the intact organ. These results also clearly indicate that diabetes in the male rat affects at least two different rate-limiting steps in the hepatic drug metabolism process.
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