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Pharmacokinetics of dexmedetomidine, MK ‐467, and their combination following intravenous administration in male cats
Author(s) -
Pypendop B. H.,
Honkavaara J.,
Ilkiw J. E.
Publication year - 2016
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12302
Subject(s) - dexmedetomidine , pharmacokinetics , volume of distribution , intravenous bolus , cats , bolus (digestion) , anesthesia , crossover study , medicine , fissipedia , pharmacology , chemistry , placebo , alternative medicine , pathology , sedation
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.