title: Pharmacokinetics and short-term clinicopathologic changes after intravenous administration of a high dose of methimazole in dogs.
abstract: 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 impart protection against cisplatin-induced renal disease. Blood and urine samples for pharmacokinetic analysis were collected over a 24-hour period. Physical examination, CBC, determination of serum thyroid hormone concentrations, and serum biochemistry analysis were performed over a 10-day period to evaluate short-term toxicoses. At this dosage, MMI 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 determined for MMI. Renal clearance of native MMI, along with sulfate and glucuronide conjugates, represented only 20% of total systemic clearance. Results of this study provide further information concerning clinical use of MMI in dogs and may contribute to better understanding of the mechanism of MMI protection against chemically induced nephrotoxicosis.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, Madison, WI 53706-1102.
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
authors.forename: A A
authors.initials: AA
authors.lastname: Elfarra
authors.forename: D L
authors.initials: DL
authors.lastname: Panciera
authors.forename: P R
authors.initials: PR
authors.lastname: Hutson
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004285:Dogs; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007668:Kidney / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate; D008713:Methimazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D010052:Ovariectomy; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood
chemical_list: D014284:Triiodothyronine; D008713:Methimazole; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D013974:Thyroxine