EFFECTS OF CHLORAMPHENICOL ON INFUSION PHARMACOKINETICS OF PROPOFOL IN GREYHOUNDS

To investigate the effect of chloramphenicol, a cytochrome P-450 inhib itor, on the pharmacokinetics of propofol, either chloramphenicol (50 mg/kg of body weight, IV) or saline solution was administered IV to 5 Greyhounds in randomized manner, with at least 2 weeks between trials. Thirty minutes after either chloramphenicol or saline treatment; a bo lus dose of propofol (10 mg/kg, IV) was administered, followed by a 2- hour infusion of propofol (0.4 mg/kg/min, IV). Samples for determinati on of blood propofol concentration were collected sequentially over a g-hour period during each trial. After termination of propofol infusio n, the time to spontaneous head lift, extubation, sternal recumbency, and standing was recorded. Blood propofol concentration was determined by use of high-performance liquid chromatography. Concentration-time data were fitted to a two-compartment open pharmacokinetic model and p harmacokinetic variables were determined, using a microcomputer progra m for modeling and simulation of concentration-time data. The effect o f chloramphenicol on the pharmacokinetics of propofol and recovery tim e were evaluated, using paired t-tests and Wilcoxon's test for paramet ers that are not normally distributed (t(1/2(beta)), V-d(ss), Cl-B) Si gnificant (P < 0.05) effects of chloramphenicol pretreatment: included increased t(1/2(beta)) (by 209%), and decreased Cl-B (by 45%), and pr olonged recovery indices (by 768 to 946%). These results indicate that cytochrome P-450 metabolic pathways have an important role in propofo l clearance and propofol anesthetic recovery in Greyhounds.