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Impairment of Prednisolone Disposition in Patients with Graves' Disease Taking Methimazole^*

Department of Endocrinology, University of Tuebingen Tuebingen, West Germany
The Department of Internal Medicine, Rhine- Westphalien University Aachen Aachen, West Germany

Address requests for reprints to: Dr. Udo F. Legler, Schwarz GmbH, Mittelstrasse 11, 4019 Monheim, West Germany.

This study was undertaken to determine the effect of methimazole on the pharmacokinetics of iv prednisolone in patients with Graves' disease. Twenty women were studied, including eight with severe infiltrative ophthalmopathy who had taken methimazole and T₄ for at least 4 months, six with severe infiltrative ophthalmopathy who had undergone subtotal thyroidectomy and, therefore, required no antithyroid treatment, and six age-matched normal women. All were euthyroid. Each women received 0.54 mg/kg prednisolone as an iv bolus dose. Plasma total and unbound prednisolone concentrations were measured at multiple times during a 10-h study period by high pressure liquid chromatography and equilibrium dialysis. The clearance of both total and unbound prednisolone was increased significantly in the women receiving methimazole therapy compared to values in both control groups. The volume of distribution at steady state was similar in all groups. These results suggest that patients receiving methimazole have enhanced prednisolone metabolism and, therefore, they may require higher prednisolone doses

^* This work was supported in part by the Deutsche Forschungsgemeinschaft (Le 435/3).

Received March 23, 1987.