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Enflurane and Methoxyflurane Metabolism at Anesthetic and at Subanesthetic Concentrations

Anne E. White, MS^*, Wendell C. Stevens, MD, Edmond I. Eger, II, MD, Richard I. Maze, MD, and Ben A. Hitt, PhD^||

*Staff Research Associate, University of California, San Francisco. Professor, University of Iowa, Iowa City, Iowa. Professor, University of California, San Francisco. Professor, Stanford University; and Chief, Anesthesiology Service, Veterans Administration Hospital, Palo Alto, California. ||Consulting Assistant Professor, Stanford University and Anesthesiology Service, Veterans Administration Hospital, Palo Alto, California. Department of Anesthesia, University of California, San Francisco, California, and Department of Anesthesia, Stanford University School of Medicine, Anesthesiology Service, Veterans Administration Hospital, Palo Alto, California. Presented at the 1975 ASA Meeting, Chicago, Illinois

Abstract

In an attempt to determine the importance of concentration of an anesthetic agent as a determinant of the extent of its biotransformation, we measured fluoride excretion in groups of Fischer 344 rats treated with one of several subanesthetic or an anesthetic concentration (1 MAC) of either enflurane or methoxyflurane. Anesthetic administrations (2.0% enflurane or 0.26% methoxyflurane) ranged from 0.15 hours (9 minutes) to 4.8 hours. Subanesthetic exposures, all of 48 hours duration, ranged in concentration from 0.2% enflurane to 0.0016% methoxyflurane. Greatest metabolism occurred at the lowest concentration time (MAC-hours) of subanesthetic administrations and at the shortest duration of anesthetic exposure. Increasing time in the case of anesthetizing exposures, or concentration in subanesthetic exposures, increased the amount of metabolite produced. However, the increased production of metabolite was not proportional to the increase of concentration or duration of exposure. Enzyme induction was ruled out as an important factor in the larger amount of metabolism seen during the subanesthetic exposures. Therefore, the exposure of a patient to the metabolites of an anesthetic is actually low although the anesthetic is administered at a high concentration.

Key Words: BIOTRANSFORMATION: enflurane • BIOTRANSFORMATION: methoxyflurane • ANESTHETICS, Volatile: enflurane • ANESTHETICS, Volatile: methoxyflurane

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999