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Pharmacokinetics of xylazine after 2‐, 4‐, and 6‐hr durations of continuous rate infusions in horses
Author(s) -
Hopster Klaus,
Soma Lawrence R.,
Li Xiaoqing,
HopsterIversen Charlotte,
Boston Raymond C.,
Driessen Bernd
Publication year - 2020
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.12873
Subject(s) - pharmacokinetics , sedation , xylazine , volume of distribution , bolus (digestion) , elimination rate constant , anesthesia , heart rate , chemistry , plasma clearance , medicine , continuous infusion , blood pressure , pharmacology , zoology , ketamine , endocrinology , biology
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 ( AUC 0 ∞ ) ( 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.