Isoniazid-induced enflurane defluorination in humans

Area of Science:

• Pharmacology
• Anesthesiology
• Clinical Chemistry

Background:

• Isoniazid is a common medication for tuberculosis.
• Enflurane is an anesthetic agent.
• Drug metabolism can vary significantly between individuals.

Purpose of the Study:

• To investigate the effect of isoniazid on serum inorganic fluoride levels in patients undergoing anesthesia with enflurane.
• To identify potential correlations between isoniazid treatment, fluoride levels, and anesthetic exposure.

Main Methods:

• Serum inorganic fluoride (F-) levels were measured in 20 surgical patients receiving isoniazid daily for up to one year before enflurane anesthesia.
• 36 control patients receiving enflurane anesthesia without isoniazid were also studied.
• Regression analysis was used to plot peak serum fluoride against enflurane exposure (MAC-hours).

Main Results:

• Nine isoniazid-treated patients exhibited significantly higher peak serum fluoride levels compared to other isoniazid patients and controls (P < 0.001).
• Peak serum fluoride exceeded 100 microM in three patients, but generally decreased below 10 microM within 48 hours post-anesthesia.
• A subset of isoniazid patients (9 out of 20) showed elevated fluoride levels, suggesting a differential response.

Conclusions:

• Isoniazid treatment can lead to elevated serum fluoride levels, likely due to enzyme induction in a subset of patients.
• The observed bimodal distribution of high fluoride levels suggests a link to the genetically determined rapid and slow acetylation of isoniazid.
• These findings highlight the importance of considering patient genetics and medication history when administering enflurane anesthesia.