Effects of hepatic P-450 enzyme inhibitors and inducers on the duration of xylazine + ketamine anesthesia in broiler chickens and mice.

We previously showed that pretreatment with inhibitors of hepatic P-450 microsomal enzymes prolonged xylazine-ketamine anesthesia, which sometimes led to mortality in rats. In this study we determined if similar effects were produced in broiler chickens and mice. A combination of 5 mg xylazine/kg and 15 mg ketamine/kg im was given to broiler chickens 5-6 w of age, and a combination of 10 mg xylazine/kg and 200 mg ketamine/kg ip was given to mice. The loss of righting reflex was used to measure duration of anesthesia. Pretreatment with 100 mg chloramphenicol/kg im, 150 mg cimetidine/kg im, 25 mg SKF-525A/kg im or 40 mg ketoconazole/kg po significantly increased the duration of xylazine + ketamine anesthesia in the chickens. Pretreatment with 40 mg phenobarbital/kg im bid for 3 d, 25 mg 3-methylcholanthrene/kg im sid for 3 d, or 50 mg rifampin/kg im bid for 2 d failed to alter the duration of xylazine + ketamine anesthesia in the broilers. None of the inhibitors tested altered the duration of anesthesia in mice. Some chickens pretreated with inhibitors (cimetidine, ketoconazole, SKF-525A) or inducers (phenobarbital, 3-MC, rifampin) died. This study suggests that hepatic metabolism of xylazine may be similar in the rat and broiler chicken and that the pulmonary metabolism of xylazine and ketamine may be different in chickens and rats.