The Effect of Phenobarbital on the Metabolism of Methimazole in the Rat^*

Abstract

The metabolism of a single dose of 35S-methimazole was studied over a 10-hr period in the thyroid, plasma and liver from both a control group of rats and a group treated with phenobarbital for 4 days. In the thyroid, there was a marked increase in the accumulation of total 35S-radioactivity accompanied by a significant increase in the oxidation of methimazole in the group receiving phenobarbital. Decreased total 35S halflives in the plasma and liver together with decreased proportions of unmetabolized methimazole were also observed. The changes in methimazole metabolism in the thyroid could possibly be due to a TSH effect mediated by phenobarbital induced changes in peripheral thyroxine turnover; thyroidal microsomal enzyme induction could also be a contributory mechanism. The changes observed in the plasma and liver could result from induction of the liver microsomal enzymes responsible for methimazole metabolism; an enhanced biliary flow is also considered as an additional mechanism. (Endocrinology95: 875, 1974)