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) (0.5 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 (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) ml min−1 kg−1, respectively. Significant differences were seen for area under the curve ( AUC0∞) (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.

Xylazine Infusion during Equine Colic Anesthesia with Isoflurane and Lidocaine: A Retrospective Study

“…The heart rate decreased and MAP increased in healthy horses for 30 min after giving a bolus and starting a xylazine infusion over 2, 4 and 6 h [ 17 ]. Reductions in minimal and average HR were indeed observed in the current study, but they might be considered clinically irrelevant since the minimal HR was 38 ± 7 beats per minute in group L and 35 ± 6 beats per minute in group XL, and the average HR was 43 ± 8 beats per minute in group L and 40 ± 7 beats per minute in group XL.…”

“…Equine colic has severe repercussions on the cardiovascular system of the animals, and might present with dehydration, blood entrapment, preload decrease, endotoxemia, reperfusion shock, etc., resulting in high variations in cardiovascular function between cases. Additionally, the chosen dose in our study was 0.5 mg/kg/h, half the dose that showed an increase in MAP, but a decrease in cardiac output [ 17 ]. The xylazine infusion was given to improve the balance of the anesthetic colic protocol in our center.…”

“…However, the time in lateral recumbency and time to first attempt to stand were significantly higher in group XL. Recently, a xylazine infusion over 2, 4 and 6 h was not associated with an accumulation in the plasma or tissues of awake non-colic horses [ 17 ]. There are no data about the influence of anesthesia and colic surgery on the pharmacokinetic and pharmacodynamic properties of xylazine.…”

“…A bolus of 0.5 mg/kg IV reduced the isoflurane MAC by 25% in healthy horses [ 15 ] and a xylazine infusion of 1 mg/kg/h decreased the need for cardiovascular support in non-colic horses [ 16 ]. A bolus of 0.5 mg/kg IV followed by an infusion of 1 mg/kg/h over 2, 4 and 6 h in healthy, awake horses caused a significant decrease in heart rate (HR) and an increment in mean arterial pressure (MAP) during the first 30 min after the bolus administration, without subsequently decreasing MAP under baseline values [ 17 ]. A similar xylazine infusion administered over 60 min in healthy isoflurane-anesthetized horses resulted in a decrease in cardiac output and oxygen delivery, without affecting measured intestinal oxygenation [ 18 ].…”