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Effects of 5,5'-diphenylhydantoin on the metabolic pathway of thyroid hormone in rats

Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels and interferes with the metabolic pathway of TH. To test the hypothesis that DPH affects the enterohepatic cycle of TH and, thus, the kinetics of TH turnover, we performed a kinetic experiment (three-compartment analysis) and a steady-state, double-isotope equilibrium experiment in rats treated for 3 weeks with DPH (50 mg/kg body weight per day) and in untreated controls. This included measurements of TH and TH metabolite levels, as well as the activities of enzymes involved in the TH metabolic pathway.

DPH treatment resulted in a decrease in the production of thyroxine (T₄) (by 25%) and triiodothyronine (T₃) (by 37%), a decrease in the T₃ concentration in all three pools, and a redistribution of T₄ from the fast to the slow pool. The amount of T₄ increased in intestinal contents and feces by 66% and 71% respectively. Expressed as a fraction of daily TH disposal, fecal loss of T₄ was enhanced from 10 to 23% and that of T₃ from 16 to 21%. An increase in T₄ and T₃ UDP-glucuronyltransferase activities was observed, suggesting that the increased fecal loss of T₄ and T₃ is secondary to an increased biliary output of their glucuronides. The reduced secretion of TH and increased fecal clearance during DPH treatment can lead in the long run to depletion of TH stores.

European Journal of Endocrinology 136 324–329

This article has been cited by other articles:

				M. Eravci, G. Pinna, H. Meinhold, and A. Baumgartner Effects of Pharmacological and Nonpharmacological Treatments on Thyroid Hormone Metabolism and Concentrations in Rat Brain Endocrinology, March 1, 2000; 141(3): 1027 - 1040. [Abstract] [Full Text] [PDF]