Pharmacokinetics and metabolic effects of triamcinolone acetonide and their possible relationships to glucocorticoid-induced laminitis in horses.
Experiments were performed to establish the pharmacokinetics of triamcinolone acetonide and the effects of the glucocorticoid on glucose metabolism in horses. The pharmacokinetics after intravenous (i.v.) dosing was best described by a three-compartment open model. There was rapid distribution from the central compartment followed by two phases of elimination. The half-life of the rapid elimination phase was 83.5 min and of the slower phase was 12 h. The term (Vss/Vc)-1was 12.3 indicating extensive distribution into the tissues. Triamcinolone acetonide given i.v. or intramuscularly (i.m. ) induced a prolonged period of hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. Significant changes in plasma glucagon and serum non-esterified fatty acids were not observed. These observations suggest that the hyperglycaemia was a result of decreased glucose utilization by tissues and increased gluconeogenesis. The effects on glucose metabolism persisted for 3-4 days after triamcinolone was given i.m. at 0.05 mg/kg, the upper limit of the recommended dose range, and for 8 days when given at 0. 2 mg/kg. These observations, together with recent evidence implicating inhibition of glucose metabolism in the pathogenesis of equine laminitis, indicated that triamcinolone-induced laminitis may be associated with the long duration of action of the glucocorticoid when higher than recommended doses or when repeated doses are given.
French
K
K
School of Veterinary Science and Animal Production, The University of Queensland, St Lucia, Qld, 4072 Australia.
Pollitt
C C
CC
Pass
M A
MA
D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005534:Foot Diseases / Q000139:chemically induced / Q000662:veterinary*; D005934:Glucagon / Q000097:blood; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006724:Hoof and Claw; D006734:Horse Diseases / Q000139:chemically induced*; D006736:Horses / Q000378:metabolism*; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007328:Insulin / Q000097:blood; D008297:Male; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007328:Insulin; D014280:Triglycerides; D005934:Glucagon; D014222:Triamcinolone Acetonide