EFFECTS OF PHENYLBUTAZONE ON THIAMYLAL DISPOSITION AND ANESTHESIA IN PONIES

Phenylbutazone given during the perisurgical period has been reported to increase the intensity and duration of thiamylal anaesthesia in hor ses. A possible mechanism of competitive plasma protein binding has be en suggested. The purpose of the present study was to experimentally r eproduce the phenomenon of increased intensity and/or duration of thia mylal anaesthesia and to determine if there is competitive displacemen t of plasma protein bound thiamylal by phenylbutazone. Six ponies each received one of three treatments, 11 mg/kg intravenous (i.v.) thiamyl al; 8.8 mg/kg i.v. phenylbutazone; and 11 mg/kg i.v. thiamylal with 8. 8 mg/kg i.v. phenylbutazone given 9 min later. Thirteen blood samples were collected from 0 time through 600 min following drug administrati on and plasma drug concentrations quantified by high performance liqui d chromatography. The pharmacokinetics of thiamylal and phenylbutazone were best described by three- and two-compartment models, respectivel y. There were no significant differences in pharmacokinetic parameters for thiamylal in the presence of phenylbutazone. However, there were differences in phenylbutazone pharmacokinetics when preceded by thiamy lal administration. Unbound phenylbutazone concentrations were increas ed at 171, 231 and 351 min when given with thiamylal, accompanied by d ecreases in per cent bound phenylbutazone (P < 0.05). There were also significant (P < 0.05) changes in per cent plasma protein binding of t hiamylal and phenylbutazone between 120 and 360 min, when in combinati on. No changes in intensity or duration of anaesthesia were observed.