title: Pharmacokinetics of ketamine and its metabolite norketamine administered at a sub-anesthetic dose together with xylazine to calves prior to castration.
abstract: The objective of this study was to evaluate the plasma pharmacokinetics of ketamine and its active metabolite norketamine administered intravenously at a dose of 0.1 mg/kg together with xylazine (0.05 mg/kg) to control the pain associated with castration in calves. A two-compartment model with an additional metabolite compartment linked to the central compartment was used to simultaneously describe the time-concentration profiles of both ketamine and its major metabolite norketamine. Parameter values estimated from the time-concentration profiles observed in this study were volume of the central compartment (V(c) = 132.82 +/- 68.23 mL/kg), distribution clearance (CL(D) = 15.49 +/- 2.56 mL/min/kg), volume of the peripheral compartment (V(T) = 257.05 +/- 41.65 mL/kg), ketamine clearance by the formation of the norketamine metabolite (CL(2M) = 8.56 +/- 7.37 mL/kg/min) and ketamine clearance by other routes (CL(o) = 16.41 +/- 3.42 mL/kg/min). Previously published data from rats suggest that the metabolite norketamine contributes to the analgesic effect of ketamine, with a potency that is one-third of the parent drug. An understanding of the time-concentration relationships and the disposition of the parent drug and its metabolite is therefore important for a better understanding of the analgesic potential of ketamine in cattle.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502, USA. rgehring@vet.ksu.edu
authors.forename: R
authors.initials: R
authors.lastname: Gehring
authors.forename: J F
authors.initials: JF
authors.lastname: Coetzee
authors.forename: J
authors.initials: J
authors.lastname: Tarus-Sang
authors.forename: M D
authors.initials: MD
authors.lastname: Apley
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics*; D000771:Anesthesia, Intravenous / Q000662:veterinary; D000778:Anesthetics, Dissociative / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D002417:Cattle / Q000097:blood / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000662:veterinary; D004338:Drug Combinations; D007649:Ketamine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009919:Orchiectomy / Q000662:veterinary; D010146:Pain / Q000188:drug therapy / Q000662:veterinary; D014991:Xylazine / Q000493:pharmacokinetics*
chemical_list: D000316:Adrenergic alpha-Agonists; D000778:Anesthetics, Dissociative; D004338:Drug Combinations; D014991:Xylazine; D007649:Ketamine; C033419:norketamine