Journal of Clinical Endocrinology & Metabolism, Vol 58, 473-479, Copyright © 1984 by Endocrine Society

ARTICLES

Methimazole pharmacology in man: studies using a newly developed radioimmunoassay for methimazole

DS Cooper, HH Bode, B Nath, V Saxe, F Maloof and EC Ridgway

A RIA for the antithyroid drug methimazole [1-methyl-2- mercaptoimidazole (MMI)] has been developed. A MMI derivative, 5-COOH- MMI, was conjugated to porcine thyroglobulin, and antibodies to the conjugate were raised in rabbits. [35S]MMI was used as the tracer. At a final antibody dilution of 1:100, the assay could detect MMI in amounts as low as 2.5 ng. The putative MMI metabolites 3-methyl-2-thiohydantoin and 1-methylimidazole had minor cross-reactivities of 2.1% and 0.5%, respectively. There was no effect of serum proteins on MMI immunoactivity. MMI was given orally to normal subjects (n = 6), hyperthyroid patients (n = 5), patients with hepatic cirrhosis (n = 4), and normal lactating women (n = 4). After a single dose of 60 mg, peak MMI levels were similar in the normal subjects and the hyperthyroid patients (approximately 1.5 micrograms/ml). Patients with hepatic cirrhosis had similar peak MMI serum levels [1.31 +/- 0.3 (+/- SEM) micrograms/ml], but the half-time of MMI disappearance from serum was significantly prolonged compared with the normal value (21.2 vs. 6.0 h; P less than 0.001). The lactating women received 40 mg MMI as a single dose. Over the next 8 h, mean MMI levels in serum and milk were nearly identical, with a mean serum to milk ratio of 1.03 +/- 0.16. A total of 70.0 +/- 6.0 micrograms MMI was excreted in the milk over the 8-h time period. This amount of MMI could affect neonatal thyroid function.

This article has been cited by other articles:

				D. S. Cooper Antithyroid Drugs N. Engl. J. Med., March 3, 2005; 352(9): 905 - 917. [Full Text] [PDF]

				D. D Streetman and U. Khanderia Diagnosis and Treatment of Graves Disease Ann. Pharmacother., July 1, 2003; 37(7): 1100 - 1109. [Abstract] [Full Text] [PDF]

				Committee on Drugs The Transfer of Drugs and Other Chemicals Into Human Milk Pediatrics, September 1, 2001; 108(3): 776 - 789. [Abstract] [Full Text] [PDF]

				S. J. Mandel and D. S. Cooper The Use of Antithyroid Drugs in Pregnancy and Lactation J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2354 - 2359. [Full Text] [PDF]

				F. Azizi, M. Khoshniat, M. Bahrainian, and M. Hedayati Thyroid Function and Intellectual Development of Infants Nursed by Mothers Taking Methimazole J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3233 - 3238. [Abstract] [Full Text]

				N. Momotani, J. Yoshimura Noh, N. Ishikawa, and K. Ito Effects of Propylthiouracil and Methimazole on Fetal Thyroid Status in Mothers with Graves' Hyperthyroidism J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3633 - 3636. [Abstract] [Full Text] [PDF]

				L. L. Toll A Review of the New AAP Guidelines on Drugs and Human Milk J Hum Lact, June 1, 1990; 6(2): 73 - 74. [PDF]