Isoniazid-induced Enflurane Defluorination in Humans

Abstract

Serum inorganic F- levels were measured in 20 surgical patients treated with 300 mg isoniazid/day for periods of up to 1 yr, prior to anesthesia with enflurane. Control patients [36] anesthetized with enflurane, but taking no drugs, were also studied. Regression lines for peak serum F- were plotted against enflurane exposure in MAC[minimum anesthetic concentration]-hours. Nine isoniazid-treated patients had F- levels significantly (P < 0.001) higher (y = 22.2x + 12.0) than either the 11 other isoniazid-treated patients (y = 5.0x + 8.2) or the 36 control patients (y = 5.4x + 6.3). Peak serum F- values in 3 patients exceeded 100 .mu.M but in no patient did values exceed 10 .mu.M by 48 h after anesthesia. Evidently, isoniazid treatment resulted in enzyme induction in the 9 patients with high peak F- levels. This pattern, i.e., induction occuring in .apprx. 1/2 the patients, probably is related to the genetically determined bimodal distribution of rapid and slow acetylation of isoniazid.