Effects of some hepatic microsomal enzyme inducers and inhibitors on xylazine-ketamine anesthesia.

Various inducers and inhibitors of hepatic microsomal enzymes were studied for their effects on xylazine-ketamine anesthesia. Pretreatment of Sprague-Dawley rats with chloramphenicol (100 mg/kg, ip), cimetidine (100 mg/kg, ip), ketoconazole (40 mg/kg, po), and SKF 525-A (25 mg/kg, ip) significantly (p less than 0.05) increased the duration of anesthesia in rats injected with ketamine (45 mg/kg, im) and xylazine (21 mg/kg, im). Pretreatment with phenobarbital (40 mg/kg, ip, once daily for 4 days) did not affect the duration of anesthesia significantly. The increase in duration of anesthesia in animals pretreated with SKF 525-A and ketoconazole was accompanied by secondary respiratory distress about 6 hr following recovery from anesthesia, often leading to death within 24 hr. Lesions consisting of extensive serous pleural effusion, alveolar edema rich in macrophages and extensive pulmonary hilar edema with hemorrhage were found at necropsy. These results indicate that inhibition of hepatic microsomal enzymes by commonly used therapeutic agents during xylazine-ketamine anesthesia to prolong the anesthetic effect, or as a result of concurrent pharmacotherapy, could have deleterious effects.