Effect of cimetidine on biotransformation of enflurane in man

This study was designed to test the hypothesis that administration of clinical doses of cimetidine could affect the metabolic degradation of enflurane to inorganic fluoride via inhibition of the mixed function oxidase enzyme (MFOE) system. In Part 1 of the study 38 female patients undergoing gynaecologic surgery received, double blind, either cimetidine, 300 mg PO the night prior to surgery and 300 mg IV 30 minutes prior to anaesthesia induction or a placebo. In Part 2, 24 patients received either cimetidine as in Part 1, but with continued administration for 24 hours into the postoperative period, or a placebo. Anaesthesia in all cases was with enflurane in oxygen, via a closed circuit. In both Parts 1 and 2 of the study there were no statistically significant differences between the two groups in serum fluoride levels at baseline, four hours or 24 hours postoperatively, or in the total urinary fluoride excretion during the first or second postoperative days. The authors speculate that this is due either to separate interactions of cimetidine and enflurane with the MFOE system or to the relatively low rate of enflurane metabolism.