title: Enantiomeric disposition of ketorolac in goats following administration of a single intravenous and oral dose.
abstract: The purpose of this study was to investigate the stereospecific pharmacokinetics of ketorolac (KT) in goats following a single 2 mg/kg intravenous (i.v.) dose and a single 6 mg/kg oral dose. A stereoselective high pressure liquid chromatography assay was used to quantify ketorolac plasma concentrations. Pharmacokinetic parameters for both stereoisomers were estimated by model independent methods. Following an i.v. dose, the plasma concentration profiles for the stereoisomers were similar with half-lives of 1.05 +/- 0.62 h for R-KT and 1.05 +/- 0.61 h for S-KT. Clearance values for R- and S-KT after an i.v. dose were 0.53 +/- 0.23 and 0.54 +/- 0.23 L.h/kg, respectively. Following an oral dose, the terminal half-lives were longer with values of 34.08 +/- 11.81 and 33.97 +/- 12.19 h for R-KT and S-KT, respectively. The average bioavailability was 133 +/- 23% for R-KT and S-KT, respectively. The longer half-lives and high apparent bioavailability after oral dosing are suggestive of a slow absorption process in the gastrointestinal tract and recycling. The results indicate that interconversion of the stereoisomers of ketorolac is absent in goats. However, studies with individual isomers are needed before any conclusion can be drawn about the lack of bioinversion.
authors.affiliation: GlaxoSmithKline, King of Prussia, PA 19406, USA. rakesh.2.nagilla@gsk.com
authors.forename: R
authors.initials: R
authors.lastname: Nagilla
authors.forename: D D
authors.initials: DD
authors.lastname: Deshmukh
authors.forename: K J
authors.initials: KJ
authors.lastname: Copedge
authors.forename: S
authors.initials: S
authors.lastname: Miller
authors.forename: B
authors.initials: B
authors.lastname: Martin
authors.forename: E C
authors.initials: EC
authors.lastname: Bell
authors.forename: S H
authors.initials: SH
authors.lastname: Duran
authors.forename: W R
authors.initials: WR
authors.lastname: Ravis
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006041:Goats / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D007262:Infusions, Intravenous / Q000662:veterinary; D007408:Intestinal Absorption; D020910:Ketorolac / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011897:Random Allocation; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D020910:Ketorolac