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  • Author or Editor: Christinia Hague x
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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.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine pharmacokinetics of IV, IM, and oral administration of cefepime in horses and to compare pharmacokinetics of IM administration of cefepime with those of ceftiofur sodium.

Animals

6 clinically normal adult horses.

Procedure

Horses received 3 doses of cefepime (11 mg/kg of body weight, PO; 2.2 mg/kg, IV; and 2.2 mg/kg, IM) and 1 dose of ceftiofur (2.2 mg/kg, IM). Two horses also received l-arginine, PO and IV, at doses identical to those contained in the cefepime dihydrochloride-l-arginine preparations previously administered. Blood samples were collected for 24 hours after administration of cefepime or ceftiofur and were assayed for cefepime and ceftiofur concentrations.

Results

Pharmacokinetic analysis of disposition data indicated that IV administration data were best described by a 2-compartment open model, whereas IM administration data were best described by a 1-compartment absorption model. Median elimination half-life and volume of distribution after IV administration of cefepime were 125.7 minutes and 225 ml/kg, respectively. After IM administration of cefepime, mean maximal plasma concentration of (8.13 μg/ml) was reached at a mean time of 80 minutes. Absorption of cefepime after IM administration was complete, with a median bioavailability of 1.11. Intramuscular administration of ceftiofur resulted in similar mean maximal plasma concentration (7.98 μg/ml) and mean time to this concentration (82 minutes). Cefepime was not detected in samples collected after oral administration. Adverse effects consisting principally of gastrointestinal disturbances were observed after oral and IM administration of cefepime and after 1 IM administration of ceftiofur.

Conclusions and Clinical Relevance

Cefepime, administered IV or IM at a dosage of 2.2 mg/kg, every 8 hours is likely to provide effective antibacterial therapy for cefepime-sensitive organisms in horses. Further studies are needed to evaluate adverse effects on the gastrointestinal tract. (Am J Vet Res 1998;59:458–463)

Free access
in American Journal of Veterinary Research