Pharmacokinetics of xylazine after 2-, 4-, and 6-hr durations of continuous rate infusions in horses

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Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg(-1) hr(-1) for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration-time curves following bolus and CRI were best described by a one-compartment model. No differences were found between pharmacokinetic estimates of the CRIs for the fractional elimination rate constant (K-e), half-life (t(1/2e)), volume of distribution (V-d), and clearance (Cl). Median and range were 0.42 (0.15-0.97)/hr, 1.68 (0.87-4.52) hr, 5.85 (2.10-19.34) L/kg, and 28.7 (19.6-39.5) ml min(-1) kg(-1), respectively. Significant differences were seen for area under the curve (

AUC0 infinity) (p <.0002) and maximum concentration (C-max) (p <.04). This indicates that with increasing duration of infusion, XYL may not accumulate in a clinically relevant way and hence no adjustments are required in a longer XYL CRI to maintain a constant level of sedation and a rapid recovery.

Original languageEnglish
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume43
Issue number6
Pages (from-to)557-564
Number of pages8
ISSN0140-7783
DOIs
Publication statusPublished - Nov 2020

    Research areas

  • behavior, continuous rate infusion, equine, pharmacokinetics, xylazine, ARTERIAL-BLOOD-PRESSURE, CONSTANT RATE INFUSION, PHARMACODYNAMICS, CELLS, ROMIFIDINE, SEDATION

ID: 258097584