Clinical Significance of Biotransformation

  • I. Rietbrock
Conference paper
Part of the Anaesthesiologie und Intensivmedizin Anaesthesiology and Intensive Care Medicine book series (A+I, volume 185)


Volatile anesthetics are not inert, but are metabolized mainly in the liver by means of a drug-metabolizing enzyme system. Hepatic and renal lesions which are sometimes observed after administration of volatile anesthetics give grounds for speculation about the role of intermediates and metabolites occurring during biotransformation [24]. The individual risk of toxic side effects can be assessed more easily if not only metabolic pathways and end products, but also the rate of metabolism is known.


Volatile Anesthetic Halothane Anesthesia Antipyrine Plasma Subsequent Lipid Peroxidation Halothane Metabolism 
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  1. 1.
    Bauereisen E (1980) Regulationsmechanismen der Leberdurchblutung. In: Weis KH, Cunitz G (eds) 25 Jahre DGAI. Springer, Berlin Heidelberg New York, p 242 (Anaesthesiologie und Intensivmedizin, vol 130 )Google Scholar
  2. 2.
    Brown BR (1971) The diphasic action of halothane on the oxidative metabolism of drugs by the liver. Anesthesiology 35: 241PubMedCrossRefGoogle Scholar
  3. 3.
    Chase RE, Holaday DA, Fiserova-Bergerova V, Saidman LJ, Mack FE (1971) The biotransformation of ethrane in man. Anesthesiology 35: 262PubMedCrossRefGoogle Scholar
  4. 4.
    Cousins MJ, Mazze RI (1973) Methoxyflurane nephrotoxicity: A Study of dose-response in man. JAMA 225: 1611PubMedCrossRefGoogle Scholar
  5. 5.
    Cousins MJ, Sharp JH, Gourlay GK, Adams JF, Haynes WD, Whitehead F (1979) Hepatoxicity and halothane metabolism in an animal model with application for human toxicity. Anaesth Intensive Care 7: 9PubMedGoogle Scholar
  6. 6.
    Danhof M, Breimer DD (1979) Studies on the different metabolic pathways of antipyrine in man. I. Oral administration of 250, 500 and 1000 mg to healthy volunteers. Br J Clin Pharmacol 8: 529PubMedGoogle Scholar
  7. 7.
    Gebhardt I, Frickel S, Rietbrock I (1985) Quantitativer Nachweis von Ethan und Penthan in der Ausatemluft. (To be published)Google Scholar
  8. 8.
    Gourlay GK, Adams JF, Cousins MJ, Sharp JH (1980) Time-course of formation of volatile reductive metabolites of halothane in humans and animal model. Br J Anaesth 52: 331PubMedGoogle Scholar
  9. 9.
    Harper MH, Collins P, Johnson B (1982) Hepatic injury following halothane, enflurane and isoflurane anesthesia in rats. Anesthesiology 56: 14PubMedCrossRefGoogle Scholar
  10. 10.
    Holaday DA, Rudofsky S, Trauhaft PS (1970) The metabolic degradation of methoxyflurane in man. Anesthesiology 33: 579CrossRefGoogle Scholar
  11. 11.
    Holaday DA, Fiserova-Bergerova V, Latto JP, Zumbiel MA (1975) Resistance of isoflurane to bio-transformation in man. Anesthesiology 43: 325PubMedCrossRefGoogle Scholar
  12. 12.
    Irestedt L (1982) Sauerstoffversorgung der Leber und Fluoridfreisetzung während Halothananaesthesie. In: Peter K, Jesch F (eds) Inhalationsanaesthesie heute und morgen. Springer Berlin Heidelberg New York, p II (Anaesthesiologie und Intensivmedizin, vol 149 )Google Scholar
  13. 13.
    Lazarus G, Rietbrock I (1980) Current knowledge on pharmacokinetics of halothane and enflurane. Acta Anaesthesiol Belg 31: 185PubMedGoogle Scholar
  14. 14.
    Maiorino RM, Sipes IG, Gandolfi AJ, Brown BR, Lind RC (1981) Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane. Anesthesiology 54: 383PubMedCrossRefGoogle Scholar
  15. 15.
    Mansuy D, Nastainczyk W, Ullrich V (1979) The mechanism of halothane binding to microsomal cytochrome P 450. Naunyn Schmiedebergs Arch Pharmacol 285: 315CrossRefGoogle Scholar
  16. 16.
    Mason Hs (1957) Mechanisms of oxygen metabolism. Adv Enzymol 19: 79Google Scholar
  17. 17.
    Mc Lain GE, Sipes IG, Brown BR (1979) An animal model of halothane hepatoxicity: roles of enzyme induction and hypoxia. Anesthesiology 51: 321CrossRefGoogle Scholar
  18. 18.
    Nastainczyk W, Ullrich V, Sies H (1978) Effect of oxygen concentration on the reaction of halothane with cytochrom P 450 in liver microsomes and isolated perfused rat liver. Biochem Pharmacol 27: 387PubMedCrossRefGoogle Scholar
  19. 19.
    Neuberger J, Davis M (1984) Advances in understanding of halothane hepatitis. Tips 4: 19Google Scholar
  20. 20.
    Plummer JL, Beckwith ALJ, Bastin FN, Adams JF, Cousins MJ, Hall P (1982) Free radical formation in vivo and hepatoxicity due to anesthesia with halothane. Anesthesiology 57: 160PubMedCrossRefGoogle Scholar
  21. 21.
    Recknagel R, Glende E (1973) Carbon tetrachloride hepatoxicity, an example of lethal cleavage. CRC Crit Rev Toxicol 2: 263CrossRefGoogle Scholar
  22. 22.
    Rehder K, Forbes J, Alter H, Hessler O, Stier A (1967) Halothane biotransformation in man. A quantitative study. Anesthesiology 28: 711PubMedCrossRefGoogle Scholar
  23. 23.
    Reynolds ES, Moslen MT (1974) Liver injury following halothane anesthesia in phenobarbital pretreated rats. Biochem Pharmacol 23: 189PubMedCrossRefGoogle Scholar
  24. 24.
    Rietbrock I (1975) Biotransformation von Inhalationsanaesthetika und ihre Bedeutung für klinische Nebenwirkungen. Anaesthesist 24: 381PubMedGoogle Scholar
  25. 25.
    Rietbrock I, Eberhard R, Greeff MvD, Breimer BB (1985) Effects of portal hypertension and hypoxia on drug metabolism, (to be published )Google Scholar
  26. 26.
    Sawyer DC, Eger EI, Bahlman SH, Cullen BF, Impelman D (1971) Concentration dependence of hepatic halothane metabolism. Anesthesiology 34: 230PubMedCrossRefGoogle Scholar
  27. 27.
    Sharp JH, Trudeil JR, Cohen EN (1979) Volatile metabolites and decomposition products of halo-thane in man. Anesthesiology 50: 2PubMedCrossRefGoogle Scholar
  28. 28.
    Stier A (1965) Der Stoffwechsel des Halothane und seine pharmakologisch-toxikologische Bedeutung. Habilitationsschrift, University of WürzburgGoogle Scholar
  29. 29.
    Van Dyke RA: Chenoweth MB (1965) Metabolism of volatile anesthetics. Anesthesiology 26: 348Google Scholar
  30. 30.
    Van Dyke RA, Wood CL (1975) In vitro studies on irreversible binding of halothane metabolite to microsomes. Drug Metab Dispos 3: 51PubMedGoogle Scholar
  31. 31.
    Welton AF, O’Neal O, Chaney LC, Aust SD (1975) Multiplicity of cytochrome P 450 hemoproteins in rat liver microsomes. J Biol Chem 250: 563Google Scholar
  32. 32.
    Widger LA, Gandolfi AJ, Van Dyke RA (1976) Hypoxia and halothane metabolism in vivo. Release of inorganic fluoride and halothane metabolite binding to cellular constituents. Anesthesiology 44: 197PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1987

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  • I. Rietbrock

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