Enhanced prednisolone elimination: a possible cause for failure of glucocorticoid therapy in Graves' ophthalmopathy.

This study was undertaken to determine the pharmacokinetics of intravenous prednisolone in patients with Graves' eye disease. 6 women with Graves' ophthalmopathy treated with prednisolone for severe endocrine exophthalmos were compared with 6 healthy female volunteers. All subjects with Graves' disease had been taking carbimazole and I-thyroxine as concurrent drugs for at least 4 months prior to study day. All subjects were euthyroid. Each subject received .54 mg/kg prednisolone as an i.v. bolus. Plasma concentrations for total and unbound prednisolone were determined by HPLC and equilibrium dialysis. Significant increase (p less than .01) in clearance values and significant decreases in half-life times (p less than .01) were found for both total and unbound prednisolone in women with Graves' disease compared with the control subjects. Volumes of distribution at steady-state were unchanged in both groups. The data suggest that patients with Graves' ophthalmopathy show an enhanced elimination for prednisolone and that is why they may need higher doses of corticoid although the function of the thyroid gland is euthyroid.