TY - JOUR

T1 - Pharmacokinetics of xylazine after 2-, 4-, and 6-hr durations of continuous rate infusions in horses

AU - Hopster, Klaus

AU - Soma, Lawrence R.

AU - Li, Xiaoqing

AU - Hopster-Iversen, Charlotte

AU - Boston, Raymond C.

AU - Driessen, Bernd

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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.

KW - behavior

KW - continuous rate infusion

KW - equine

KW - pharmacokinetics

KW - xylazine

KW - ARTERIAL-BLOOD-PRESSURE

KW - CONSTANT RATE INFUSION

KW - PHARMACODYNAMICS

KW - CELLS

KW - ROMIFIDINE

KW - SEDATION

U2 - 10.1111/jvp.12873

DO - 10.1111/jvp.12873

M3 - Journal article

C2 - 32424949

VL - 43

SP - 557

EP - 564

JO - Journal of Veterinary Pharmacology and Therapeutics

JF - Journal of Veterinary Pharmacology and Therapeutics

SN - 0140-7783

IS - 6

ER -