Effects of chloramphenicol on infusion pharmacokinetics of propofol in Greyhounds

Ronald E. Mandsager From the Departments of Medicine and Surgery (Mandsager, Shawley) and Physiological Sciences (Clarke, Hague), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

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Cyril R. Clarke From the Departments of Medicine and Surgery (Mandsager, Shawley) and Physiological Sciences (Clarke, Hague), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

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Richard V. Shawley From the Departments of Medicine and Surgery (Mandsager, Shawley) and Physiological Sciences (Clarke, Hague), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

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Christinia M. Hague From the Departments of Medicine and Surgery (Mandsager, Shawley) and Physiological Sciences (Clarke, Hague), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

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SUMMARY

To investigate the effect of chloramphenicol, a cytochrome P-450 inhibitor, 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 bolus 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 determination of blood propofol concentration were collected sequentially over a 6-hour period during each trial. After termination of propofol infusion, 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 pharmacokinetic variables were determined, using a microcomputer program for modeling and simulation of concentration-time data. The effect of chloramphenicol on the pharmacokinetics of propofol and recovery time were evaluated, using paired t-tests and Wilcoxon's test for parameters that are not normally distributed (t½(β), Vd(ss), ClB). Significant (P < 0.05) effects of chloramphenicol pretreatment included increased t1/2(β) (by 209%), and decreased ClB (by 45%), and prolonged recovery indices (by 768 to 946%). These results indicate that cytochrome P-450 metabolic pathways have an important role in propofol clearance and propofol anesthetic recovery in Greyhounds.

SUMMARY

To investigate the effect of chloramphenicol, a cytochrome P-450 inhibitor, 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 bolus 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 determination of blood propofol concentration were collected sequentially over a 6-hour period during each trial. After termination of propofol infusion, 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 pharmacokinetic variables were determined, using a microcomputer program for modeling and simulation of concentration-time data. The effect of chloramphenicol on the pharmacokinetics of propofol and recovery time were evaluated, using paired t-tests and Wilcoxon's test for parameters that are not normally distributed (t½(β), Vd(ss), ClB). Significant (P < 0.05) effects of chloramphenicol pretreatment included increased t1/2(β) (by 209%), and decreased ClB (by 45%), and prolonged recovery indices (by 768 to 946%). These results indicate that cytochrome P-450 metabolic pathways have an important role in propofol clearance and propofol anesthetic recovery in Greyhounds.

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