Effects of phenylbutazone on thiamylal disposition and anaesthesia in ponies.
Phenylbutazone given during the perisurgical period has been reported to increase the intensity and duration of thiamylal anaesthesia in horses. A possible mechanism of competitive plasma protein binding has been suggested. The purpose of the present study was to experimentally reproduce the phenomenon of increased intensity and/or duration of thiamylal anaesthesia and to determine if there is competitive displacement of plasma protein bound thiamylal by phenylbutazone. Six ponies each received one of three treatments, 11 mg/kg intravenous (i.v.) thiamylal; 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 administration and plasma drug concentrations quantified by high performance liquid chromatography. The pharmacokinetics of thiamylal and phenylbutazone were best described by three- and two-compartment models, respectively. 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 thiamylal administration. Unbound phenylbutazone concentrations were increased at 171, 231 and 351 min when given with thiamylal, accompanied by decreases in per cent bound phenylbutazone (P < 0.05). There were also significant (P < 0.05) changes in per cent plasma protein binding of thiamylal and phenylbutazone between 120 and 360 min, when in combination. No changes in intensity or duration of anaesthesia were observed.
Young
D B
DB
Department of Medicine, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
Ewing
P J
PJ
Burrows
G E
GE
Lessley
B A
BA
Clarke
C R
CR
Shawley
R V
RV
D000758:Anesthesia / Q000662:veterinary*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006736:Horses / Q000502:physiology*; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D008954:Models, Biological; D016011:Normal Distribution; D010653:Phenylbutazone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013840:Thiamylal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D001798:Blood Proteins; D013840:Thiamylal; D010653:Phenylbutazone