Wednesday, December 26, 2012

Would Methimazole Be More Effective Given 3 Times Daily?

I have a hyperthyroid cat being treated with methimazole who is difficult to control. Are there any studies comparing the effectiveness of methimazole given 3 times daily (8 hours) versus twice daily?

I know that the plasma half-life of the drug is relatively short so it makes sense to me that giving the medication more frequently should be more effective.

My Response:

It is clear that twice daily administration of methimazole to cats with hyperthyroidism works much better than only once daily administration (1). No studies have been done in hyperthyroid cats to evaluate the effect of methimazole three times daily.

Pharmacokinetics studies of methimazole in cats document that the drug has a relatively short elimination half-life in the circulation— the average serum half-life of methimazole is only 6-7 hours (2,3). Therefore, one might think that giving the drug 3 or even 4 times a day might be more effective in normalizing the high serum T4 and T3 concentrations in cats with hyperthyroidism. However, most cat owners would not be thrilled about medicating their cat at 6- to 8-hour intervals, and fortunately, administrating methimazole more than twice a day should not ever be necessary.

After absorption, methimazole circulates in the plasma and gets taken up by the cat's thyroid tumor where the drug acts to block thyroid hormone secretion. Because methimazole is concentrated in the thyroid after administration, the intrathyroidal residence time of the drug is considerably longer than serum half-life. In studies of human patients, an intrathyroidal residence time of 24 hours or longer has been documented (4-6). Therefore, the "duration of action" of methimazole within the thyroid tumor becomes much more valuable than does the serum half-life in determining dosing schedules.

Bottom Line

The serum elimination half-life of the methimazole is relatively short in cats, but the residence time of the drug within the thyroid gland is much longer.

Although giving methimazole 3 times a day is not contraindicated, it's probably not going to help any more than simply giving a higher dose twice a day because the residence time appears to be longer than 12 hours in all hyperthyroid cats.

Methimazole is available as the human preparation, Tapazole, as well as the veterinary formulation, Felimazole.
  1. Trepanier LA, Hoffman SB, Kroll M, et al. Efficacy and safety of once versus twice daily administration of methimazole in cats with hyperthyroidism. J Am Vet Med Assoc 2003;222:954-958.    
  2. Trepanier LA, Peterson ME, Aucoin DP. Pharmacokinetics of methimazole in normal cats and cats with hyperthyroidism. Res Vet Sci 1991;50:69-74. 
  3. Trepanier LA, Peterson ME, Aucoin DP. Pharmacokinetics of intravenous and oral methimazole following single- and multiple-dose administration in normal cats. J Vet Pharmacol Ther 1991;14:367-373. 
  4. Okuno A, Yano K, Inyaku F, et al. Pharmacokinetics of methimazole in children and adolescents with Graves' disease. Studies on plasma and intrathyroidal concentrations. Acta Endocrinol (Copenh) 1987;115:112-118. 
  5. Jansson R, Dahlberg PA, Johansson H, et al. Intrathyroidal concentrations of methimazole in patients with Graves' disease. J Clin Endocrinol Metab 1983;57:129-132. 
  6. Huang G. Relation between the dosage of methimazole and its intrathyroidal concentrations. Zhonghua Yi Xue Za Zhi 1991;71:301-303, 322. 

No comments: