Biotransformation of sevoflurane

Anesthesia and Analgesia
E D Kharasch

Abstract

Several characteristics of sevoflurane biotransformation are apparent from the preceding investigations. Metabolism is rapid, with fluoride and HFIP appearing in plasma within minutes after the start of sevoflurane administration (38-40,51). Peak plasma fluoride concentrations generally occur within approximately 1 h after the termination of sevoflurane administration in most patients, regardless of the dose or duration of exposure (ranging from 0.35-9.5 MAC-h) (39,48). Peak plasma inorganic fluoride concentrations are proportional to sevoflurane dose, measured in MAC-h (42-44). Inorganic fluoride concentrations decline rapidly after termination of sevoflurane administration, with concentrations well below peak levels by the first postoperative day. HFIP is rapidly conjugated, with more than 85% circulating in plasma as the glucuronide. Plasma HFIP concentrations peak later than fluoride concentrations, but both metabolites are eliminated at similar rates (52). Metabolism of sevoflurane does not contribute to the termination of clinical drug effect (52), unlike more extensively metabolized drugs such as halothane (55). Sevoflurane is metabolized by P-450 2E1, so pathophysiologic factors and drug interactions altering P-450 2E1 ...Continue Reading

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