Abstract

Methimazole-2-¹⁴C was administered to Sprague-Dawley rats, of either sex, i.v., i.p. or p.o. at a dose of 20 mg/kg. The drug was completely absorbed after oral administration. Equilibrium dialysis indicated that 5% of the drug was bound to plasma proteins. The drug was not found to have an affinity for any particular tissue. Methimazole was found to have a much greater chloroform/water partition coefficient and water solubility than propylthiouracil. Between 77 and 95% of the administered radioactivity was excreted into the urine and approximately 10% appeared in the bile. Since negligible radioactivity was excreted into the feces, an enterohepatic circulation was present. The half-life of urinary excretion of radioactivity was five to seven hours regardless of the route of administration. Fourteen to 21% of the administered dose was excreted unchanged in the 24-hour urine. The major urinary metabolite was methimazole glucuronide, which accounted for 36 to 48% of the administered dose in 24-hour urine samples. The only other urinary metabolite, which accounted for 10 to 20% of the dose in 24 hours, has not yet been characterized. The major biliary metabolite was determined to be methimazole glucuronide and was identical to the glucuronide conjugate found in urine samples. Two other unidentified metabolites appeared in the bile, one of which is identical to the unidentified urinary metabolite.