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Impairment of prednisolone disposition in patients with Graves' disease taking methimazole
1Department of Endocrinology, University of Tuebingen, West Germany.
Abstract:
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.
Insights
Methimazole significantly increases prednisolone clearance in Graves' disease patients, suggesting enhanced metabolism. This may necessitate higher prednisolone doses for effective treatment in patients on methimazole therapy.
Area of Science:
- Pharmacology
- Endocrinology
- Clinical Medicine
Background:
- Graves' disease is an autoimmune disorder affecting the thyroid.
- Prednisolone is a corticosteroid used to manage various inflammatory and autoimmune conditions.
- Methimazole is a common antithyroid medication used to treat hyperthyroidism in Graves' disease.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between methimazole and prednisolone.
- To determine if methimazole influences the metabolism and clearance of prednisolone in patients with Graves' disease.
Main Methods:
- Twenty euthyroid women with Graves' disease (including those on methimazole, post-thyroidectomy, and normal controls) received an intravenous prednisolone dose.
- Plasma concentrations of total and unbound prednisolone were quantified over 10 hours using high-performance liquid chromatography and equilibrium dialysis.
Main Results:
- Prednisolone clearance (both total and unbound) was significantly higher in women receiving methimazole compared to control groups.
- The volume of distribution of prednisolone at steady state remained consistent across all study groups.
Conclusions:
- Methimazole therapy is associated with enhanced prednisolone metabolism in Graves' disease patients.
- Higher doses of prednisolone may be required for patients with Graves' disease who are concurrently treated with methimazole to achieve therapeutic efficacy.