Pharmacokinetics and pharmacodynamic effects of tolazoline following intravenous administration to horses

Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse

“…In the current study, the median clearance, volume of distribution and t 1/2el for tolazoline when administered subsequent to detomidine were 10.7 mL minute −1 kg −1 , 1.72 L kg −1 and 3.37 hours, respectively. A group receiving only tolazoline was not included in the current study so it is not possible to assess whether detomidine affects the disposition of tolazoline, however, t 1/2el , Vd ss and Cl are in close agreement with that reported previously for tolazoline administered as a sole agent to the horse (Casbeer & Knych ). It should be noted, though that the t 1/2el (1 hour) differs significantly from that reported by Plumb () when tolazoline is administered alone.…”

“…Plasma yohimbine and tolazoline concentrations were measured using Liquid Chromatography‐Mass spectrometry as reported previously (DiMaio Knych et al. ; Knych & Stanley ; Casbeer & Knych ). Analytical reference standards for atipamezole, and internal standards (IS) medetomidine, were obtained from Sigma Aldrich (MO, USA) and Orion (Farmos, Finland), respectively.…”

A review of clinical approaches to antagonism of alpha2‐adrenoreceptor agonists in the horse

“…Tolazoline, yohimbine and atipamezole (both central and peripheral acting α 2 ‐antagonists) are available in most countries and have been used to antagonise the α 2 ‐agonists in horses (Knych and Stanley ). Only tolazoline has been approved by the Food and Drug Administration (FDA) in the United States of America for reversal of xylazine effects in horses (Casbeer and Knych ). Yohimbine is classified as a Class 2 foreign substance by the Association of Racing Commissioners International (ARCI) (DiMaio Knych et al .…”

“…Tolazoline is a synthetic imidazoline derivative that antagonises α‐adrenoceptors nonselectively (Casbeer and Knych ) and possesses histaminergic and cholinergic effects (El‐Kammar and Gad ). Tolazoline administered i.v.…”

“…at 4 mg/kg bwt alone has the following pharmacokinetic profile: systemic clearance, steady state volume of distribution and terminal elimination half‐life of 0.82 ± 0.18 l/h/kg, 1.68 ± 0.38 l/kg and 2.69 ± 0.21 h, respectively (Casbeer and Knych ). The pharmacodynamic profile when tolazoline is administered alone demonstrates minimal behavioural responses; a decreased heart rate (most likely due to the increased sympathetic tone raising blood pressure and stimulating a baroreceptor mediated increase in vagal tone) with second degree atrioventricular blocks; an increase in blood glucose level and packed cell volume (increased sympathetic tone causing splenic contraction) and unchanged head‐height‐above‐ground (measurement used to determine the level of sedation in horses) compared to baseline readings (Casbeer and Knych ). Tolazoline, in isoflurane‐anaesthetised (Matthews et al .…”