title: Pharmacokinetics of ketorolac after intravenous and oral single dose administration in dogs.
abstract: The pharmacokinetics of ketorolac (Toradol), a human non-narcotic, nonsteroidal anti-inflammatory drug (NSAID) of the pyrrolo-pyrrole group, was studied in six mixed breed dogs of varying ages (1-5 years). The study was performed using a randomized crossover design, with each dog initially assigned to one of two groups (intravenous (i.v.) or oral (p.o.)). Each group of three dogs received either the injectable or oral formulation of ketorolac tromethamine at 0.5 mg/kg. Serial blood samples were collected before and over 96 h following treatment. Samples were analysed by reverse phase HPLC. Individual ketorolac plasma concentration-time curves were initially evaluated by computerized curve stripping techniques followed by nonlinear least squares regression. Following i.v. administration mean (+/- SD) pharmacokinetic parameters were: elimination half-life (t1/2 beta) = 4.55 h, plasma clearance (Clp) = 1.25 (1.13) mL/kg/min, and volume of distribution at steady state (Vss) = 0.33 (0.10) L/kg. Mean (+/- SD) p.o. pharmacokinetic values were: t1/2 beta = 4.07 h, time to reach maximum concentration (tmax) = 51.2 (40.6) min, and p.o. bioavailability (F) = 100.9 (46.7)%. These results suggest that the pharmacodisposition characteristics of a clinically effective 0.5 mg/kg i.v. or p.o. single dose of ketorolac tromethamine administered to dogs is fairly similar to that observed in humans.
authors.affiliation: Merck & Co., Inc., Somerville, NJ 08876, USA.
authors.forename: K
authors.initials: K
authors.lastname: Pasloske
authors.forename: R
authors.initials: R
authors.lastname: Renaud
authors.forename: J
authors.initials: J
authors.lastname: Burger
authors.forename: P
authors.initials: P
authors.lastname: Conlon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004285:Dogs; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D020910:Ketorolac / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020910:Ketorolac