Isoniazid-induced enflurane defluorination in humans

Serum inorganic fluoride (F-) levels were measured in 20 surgical patients treated with 300 mg isoniazid per day for periods of up to one year, prior to anesthesia with enflurane. Thirty-six control patients anesthetized with enflurane, but taking no drugs, also were studied. Regression lines for peak serum fluoride were plotted against enflurane exposure in MAC-hours. Nine isoniazid-treated patients had fluoride levels significantly (P less than 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 fluoride values in three patients exceeded 100 microM but in no patient did values exceed 10 microM by 48 h after anesthesia. It was concluded that isoniazid treatment resulted in enzyme induction in the nine patients with high peak fluoride levels. This pattern, i.e., induction occurring in approximately one-half the patients, probably is related to the genetically determined bimodal distribution of rapid and slow acetylation of isoniazid.