PHARMACOKINETICS AND SHORT-TERM CLINICOPATHOLOGICAL CHANGES AFTER INTRAVENOUS ADMINISTRATION OF A HIGH-DOSE OF METHIMAZOLE IN DOGS

A bolus dose of methimazole (MMI) was administered IV over 1 minute to 5 healthy adult dogs at a dosage (40 mg/kg of body weight) known to i mpart protection against cisplatin-induced renal disease. Blood and ur ine samples for pharmacokinetic analysis were collected over a 24-hour period. Physical examination, csc, determination of serum thyroid hor mone concentrations, and serum biochemistry analysis were performed ov er a 10-day period to evaluate short-term toxicoses. At this dosage, M MI appears to be safe and well tolerated in dogs; only 1 of the 5 dogs had mild and transient increases in serum activity of hepatic enzymes . In addition, MMI did not alter serum thyroid hormone concentrations. Half-life of 8.82 hours and mean residence time of 12.18 hours were d etermined for MMI. Renal clearance of native MMI, along with sulfate a nd glucuronide conjugates, represented only 20% of total systemic clea rance. Results of this study provide further information concerning cl inical use of MMI in dogs and may contribute to better understanding o f the mechanism of MMI protection against chemically induced nephrotox icosis.