Romifidine levels in plasma and red blood cells after intravenous administration in horses: preliminary study

The aim of this study was to define the levels of romifidine in plasma and red blood cells (RBCs) after intravenous (IV) administration in horses. RBCs kinetics may be relevant in haematic disease (Hinderling 1997). Ten healthy horses (weighing 380\ub121 kg, aged 3-16 years) undergoing elective surgery were used. Horses were sedated with acepromazine (0.04 mg kg-1) and romifidine (0.08 mg kg-1) intravenously.Anaesthesia was induced with ketamine (2.2mg kg-1) and midazolam (0.06 mg kg-1) and maintained with isoflurane in 100%oxygen. Venous blood samples were collected fromleft jugular vein in heparinised tubes before any drug administration, and at 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180minutes after romifidine administration. The concentration of romifidine in plasma and RBCs was determined using modified high performance liquid chromatography described by Gross et al. (1999). After IV administration the concentration of romifidine quickly decreased; distribution half life time (t1/2β) was 1.87 \ub10.64 minutes in plasma and 2.25\ub11.47 minutes in RBCs. The terminal half-life (t1/2β) was 69.64\ub133.96 minutes and 139.99\ub158.59 minutes in plasma and RBCs, respectively. The area under the curve (AUC) was 3768\ub12326 ng minutes mL-1 for plasma and 11063\ub18441 ng minutes mL-1 for RBCs. The maximum concentration (Cmax) was 331\ub1190 ng mL-1 and 575\ub1381 ng mL-1 for plasma and RBC respectively. The study shows the kinetics of romifidine in plasma and in RBCs. The half life is short both in plasma and RBCs. The most important finding was a t1/2β value of RBCs double than that of plasma. Romifidine found in the corpuscular fraction of blood could represent reservoir of the molecule. The slow release of romifidine in blood could be the reason for its very long sedative effect described by some authors (Roncada et al. 2003). Hinderling PH (1997) Red Blood Cells: a neglected compartment in pharmacokinetic and pharmacodynamics. Pharmacological Rev 49, 279-295. Gross AS, Nicolay A, Eschalier A (1999) Simultaneous analysis of ketamine and bupivacaine in plasma by high-performance liquid chromatography. J Chromatogr B 728, 107-115. Roncada P, Nigro V, Romagnoli N et al. (2003) Romifidine in the anaesthesiologic protocol in the horse: a comparison between pharmacokinetic parameters and clinical aspects. J Vet Pharmacol Ther 26, 210 (abstract)