Halothane Inhibits Metabolism of Enflurane in Fischer 344 Rats

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Abstract
The effect of prior administration of halothane upon the metabolism of enflurane was investigated. One-year-old male Fischer 344 rats (24) were assigned randomly to 4 anesthetic exposure groups. Groups 1 and 2 were controls exposed only to halothane and enflurane, respectively. Group 3 was exposed for 1 h to 0.3% halothane, followed by 2 h of 1% enflurane. Group 4 was exposed for 1 h to 1% halothane and then to 2 h of 1% enflurane. Blood samples were taken prior to, immediately following, and 4, 24 and 48 h after anesthetic exposure. Serum was assayed for inorganic fluoride (F-), SGOT and SGPT [serum glutamic oxaloacetic transaminase and serum glutamine pyruvic transaminase]. Twenty-four hour urinary collections were assayed for F- excretion. Group 1 rats exposed to halothane alone had the lowest peak mean serum F- (5.0 .mu.M). Group 2 rats exposed to enflurane alone had the highest serum F- concentration 4 h after anesthesia (18.7 .mu.M). Peak serum F- in group 3 rats (9.5 .mu.M) was significantly lower than in group 2 rats (enflurane control). In group 4 rats, serum F- was not significantly different from group 1 rats (halothane control) at any time. In the first 24 h after anesthetic exposure, urinary F- excretion in groups 2 and 3 was significantly higher than in groups 1 and 4. Prior exposure to halothane reduced the metabolism of enflurane, perhaps due to an interaction of halothane with hepatic cytochrome P-450. These results have implications for other drugs that are administered during anesthesia and are metabolized by the hepatic mixed function oxidase system.