title: Pharmacokinetics of dexmedetomidine, MK-467, and their combination following intravenous administration in male cats.
abstract: This study characterized the pharmacokinetics of dexmedetomidine, MK-467, and their combination following intravenous bolus administration to cats. Seven 6- to-year-old male neutered cats, weighting 5.1 ± 0.7 kg, were used in a randomized, crossover design. Dexmedetomidine [12.5 (D12.5) and 25 (D25) μg/kg], MK-467 [300 μg/kg (M300)] or dexmedetomidine (25 μg/kg) and MK-467 [75, 150, 300 or 600 μg/kg-only the plasma concentrations in the 600 μg/kg group (D25M600) were analyzed] were administered intravenously, and blood was collected until 8 hours thereafter. Plasma drug concentrations were analyzed using liquid chromatography/mass spectrometry. A two-compartment model best fitted the data. Median (range) volume of the central compartment (mL/kg), volume of distribution at steady state (mL/kg), clearance (mL min/kg) and terminal half-life (min) were 342 (131-660), 829 (496-1243), 14.6 (9.6-22.7) and 48 (40-69) for D12.5; 296 (179-982), 1111 (908-2175), 18.2 (12.4-22.9) and 52 (40-76) for D25; 653 (392-927), 1595 (1094-1887), 22.7 (18.5-36.4) and 48 (35-60) for dexmedetomidine in D25M600; 117 (112-163), 491 (379-604), 3.0 (2.0-4.5) and 122 (99-139) for M300; and 147 (112-173), 462 (403-714), 2.8 (2.1-4.8) and 118 (97-172) for MK-467 in D25M600. MK-467 moderately but statistically significantly affected the disposition of dexmedetomidine, whereas dexmedetomidine minimally affected the disposition of MK-467.
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Pypendop
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Honkavaara
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Ilkiw
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D002415:Cats; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D011807:Quinolizines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D011807:Quinolizines; C055732:vatinoxan; D020927:Dexmedetomidine