Pharmacokinetics and pharmacodynamic effects of tolazoline following intravenous administration to horses

Tolazoline is an alpha(2)-adrenergic receptor antagonist, used in veterinary medicine to antagonize the central nervous system depressant and cardiovascular effects of alpha(2) receptor agonists. The pharmacokinetics and pharmacodynamic effects of tolazoline when administered subsequent to detomidine in the horse were recently reported, although the reversal of the sedative and cardiovascular effects following detomidine may not be complete. The current study therefore investigated the pharmacokinetics and pharmacodynamic effects of tolazoline when administered as a sole agent. Nine healthy adult horses were administered tolazoline (4 mg/kg IV) and blood samples were collected at time 0 (prior to drug administration) and at various times up to 72 h post drug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry and resulting data analyzed using compartmental analysis. Systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.820 +/- 0.182 L/h/kg, 1.68 +/- 0.379 L/kg and 2.69 +/- 0.212 h, respectively. Tolazoline administration had no effect on chin to ground distance, but the heart rate decreased (relative to baseline) and the percentage of atrial-ventricular block increased in all horses within 2 min of administration. Packed cell volume and glucose concentrations were also increased throughout the sampling period. While not commonly used as a sole agent, caution is indicated whenever tolazoline is administered since the effects may be unpredictable. (C) 2013 Elsevier Ltd. All rights reserved.