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

Abstract

Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5mg/kg) immediately followed by a continuous rate infusion (CRI) of 1mgkg-1 hr-1 for 2, 4, and 6hr 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 15min 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 (Ke ), half-life (t1/2e ), volume of distribution (Vd ), 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)mlmin-1 kg-1 , respectively. Significant differences were seen for area under the curve ( ) (p<.0002) and maximum concentration (Cmax ) (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.