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Enantioselective effects of experimental diabetes mellitus on the metabolism of ibuprofen

X Oian and SD Hall

Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.

Diabetes mellitus is associated with numerous metabolic events that may influence the elimination of R- and S-ibuprofen and the inversion of R- ibuprofen. Short (3 days) and long (14 days) term experimental type I diabetes was induced in male Sprague-Dawley rats with streptozotocin, and genetically diabetic male Zucker rats were used as a model of type II diabetes. Isolated hepatocytes from long-term streptozotocin-treated rats exhibited significantly greater rate constants for ibuprofenyl- coenzyme A (CoA) formation (1.44 +/- 0.05 vs. 0.60 +/- 0.09 hr-1) and the elimination of R-ibuprofen (0.34 +/- 0.07 vs. 0.22 +/- 0.07 hr-1) relative to control (P < or = .05). These increases were consistent with significant induction of hepatic cytochrome P450 (1.14 +/- 0.45 vs. 0.54 +/- 0.10 nmol/mg protein) and an elevated hepatic free CoA content (313.4 +/- 48.5 vs. 172.9 +/- 38.6 nmol/g) relative to control (P < or = .05). In hepatocytes from type II diabetic rats there were significant reductions (P < or = .05) in the rate constants for ibuprofenyl-CoA formation (1.02 +/- 0.12 vs. 1.22 +/- 0.12 hr-1), R- ibuprofen elimination (0.21 +/- 0.06 vs. 0.34 +/- 0.10 hr-1) and S- ibuprofen elimination (0.41 +/- 0.07 vs. 0.73 +/- 0.11 hr-1) but no change in hepatic content of cytochrome P450 or CoA relative to control. The activity of ibuprofenyl-CoA synthetase in whole liver homogenate supplemented with ATP and CoA was not influenced by experimental diabetes. In both type I and type II diabetes there was a significantly greater exposure of hepatocytes to ibuprofenyl- CoA.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 274, Issue 3, pp. 1192-1198, 09/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


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J. C. Poggi, G. R. Barissa, E. A. Donadi, M. C. Foss, F. de Queiroz Cunha, V. L. Lanchote, and M. L. d. Reis
Pharmacodynamics, chiral pharmacokinetics, and pharmacokinetic-pharmacodynamic modeling of fenoprofen in patients with diabetes mellitus.
J. Clin. Pharmacol., November 1, 2006; 46(11): 1328 - 1336.
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