Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4

Drug Metabolism and Disposition

Volumn 24, Issue 9, 1996, Pages 976-983

  Spracklin, Douglas K ^a   Thummel, Kenneth E ^a   Kharasch, Evan D ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 METHYLPYRAZOLE; ALKANE DERIVATIVE; ALKENE DERIVATIVE; ALPHA NAPHTHOFLAVONE; ANESTHETIC AGENT; CARBON MONOXIDE; COUMARIN; CYTOCHROME P450 ISOENZYME; DIETHYLDITHIOCARBAMIC ACID; DRUG METABOLITE; ENZYME INHIBITOR; FURAFYLLINE; HALOTHANE; KETOCONAZOLE; METHOXSALEN; ORPHENADRINE; QUINIDINE; SULFAPHENAZOLE; TROLEANDOMYCIN; VOLATILE ORGANIC COMPOUND;

ARTICLE; DRUG METABOLISM; DRUG TRANSFORMATION; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN TISSUE; LIVER MICROSOME METABOLISM; PRIORITY JOURNAL; RECOMBINANT DNA TECHNOLOGY; REDUCTION;

ANESTHETICS, INHALATION; ARYL HYDROCARBON HYDROXYLASES; CARBON MONOXIDE; CHLOROFLUOROCARBONS; COUMARINS; CYTOCHROME P-450 ENZYME SYSTEM; HALOTHANE; HUMANS; ISOENZYMES; KETOCONAZOLE; KINETICS; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; RECOMBINANT PROTEINS;

EID: 0029809856     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (37)

1. J. Gut, U. Christen, N. Frey, V. Koch, and D. Stoffler: Molecular mimicry in halothane hepatitis: biochemical and structural characterization of lipoylated autoantigens. Toxicology 97, 199-224 (1995).
2. J. Gut, U. Christen, and J. Huwyler: Mechanisms of halothane toxicity: novel insights. Pharmacol. Ther. 58, 133-155 (1993).
3. J. L. Raucy, J. C. Kraner, and J. M. Lasker: Bioactivation of halogenated hydrocarbons by cytochrome P4502E1. Crit. Rev. Toxicol. 23, 1-20 (1993).
4. D. C. Ray and G. B. Drummond: Halothane hepatitis. Br. J. Anaesth. 67, 84-99 (1991).
5. M. Morio, O. Yuge, and K. Fijii: Biotransformation and toxicity of inhalational anaesthetics. Can. J. Anaesth. 37, (Suppl.) cxvi-cxx (1990).
6. G. Urban, P. Speerschneider, and W. Dekant: Metabolism of the chlorofluorocarbon substitute 1,1-dichloro-2,2,2-trifluoroethane by rat and human liver microsomes: The role of cytochrome P450 2E1. Chem. Res. Toxicol. 7, 170-176 (1994).
7. R. M. Brown, T. Taleishi, F. P. Guengerich, M. Wood, and A. J. J. Wood: Halothane microsomal oxidation is inhibited by diethyldithiocarbamate, an inhibitor of CYP2E1. Anesth. Analg. 80, S59 (1995).
8. E. D. Kharasch, D. C. Hankins, D. Mautz, and K. E. Thummel: Identification of the human enzyme responsible for halothane metabolism: implications for the prevention of halothane hepatitis. Lancet 347, 1367-1371 (1996).
9. M. Manno, R. Ferrara, S. Cazzaro, P. Rigotti, and E. Ancona: Suicidal inactivation of human cytochrome P-450 by carbon tetrachloride and halothane in vitro. Pharmacol. Toxicol. 70, 13-18 (1992).
10. M. T. Baker, M. T. Vasquez, and C.-K. Chiang: Evidence for the stability and cytochrome P450 specificity of the phenobarbital-induced reductive halothane-cytochrome P450 complex formed in rat hepatic microsomes. Biochem. Pharmacol. 41, 1691-1699 (1991).
11. N. Sato, K. Fujii, O. Yuge, and M. Morio: The association of halothane-induced lipid peroxidation with the anaerobic metabolism of halothane: an in vitro study in guinea pig liver microsomes. Hiroshima J. Med. Sci. 39, 1-6 (1990).
12. S. Akita, M. Kawahara, T. Takeshita, M. Morio, and K. Fujii: Halothane-induced hepatic microsomal lipid peroxidation in guinea pigs and rats. J. Appl. Toxicol. 9, 9-14 (1989).
13. H. de Groot and T. Noll: Halothane hepatotoxicity: relation between metabolic activation, hypoxia, covalent binding, lipid peroxidation and liver cell damage. Hepatology 3, 601-606 (1983).
14. 2-isoprostanes. Anesthesiology 84, 910-916 (1996).
15. M. J. Cousins, G. K. Gourlay, K. M. Knights, P. M. Hall, C. A. Lunam, and P. O'Brien: A randomized prospective controlled study of the metabolism and hepatotoxicity of halothane in humans. Anesth. Analg. 66, 299-308 (1987).
16. S. Gelman, E. Dillard, and E. L. Bradley: Hepatic circulation during surgical stress and anesthesia with halothane, isoflurane, or fentanyl. Anesth. Analg. 66, 936-943 (1987).
17. E. D. Kharasch and K. E. Thummel: Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane and methoxyflurane. Anesthesiology 79, 795-807 (1993).
18. O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall: Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265-275 (1951).
19. R. W. Estabrook, J. Peterson, J. Baron, and J. Hildebrandt: The spectrophotometric measurement of turbid suspensions of cytochromes associated with drug metabolism. Methods Pharmacol. 2, 303-350 (1972).
20. J. S. Miles, A. W. McLaren, L. M. Forrester, M. J. Glancey, M. A. Lang, and C. R. Wolf: Identification of the human liver cytochrome P-450 responsible for coumarin 7-hydroxylase activity. Biochem. J. 267, 365-371 (1990).
21. K. S. Lown, J. C. Kolars, K. E. Thummel, J. L. Barnett, K. L. Kunze, S. A. Wrighton, and P. B. Watkins: Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: lack of prediction by the erythromycin breath test. Drug Metab. Dispos. 22, 947-955 (1995).
22. K. E. Thummel, E. D. Kharasch, T. Podoll, and K. Kunze: Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1. Drug Metab. Dispos. 21, 350-357 (1993).
23. H. Yamazaki, Y. Inui, C.-H. Yun, F. P. Guengerich, and T. Shimada: Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes. Carcinogenesis (Lond.) 13, 1789-1794 (1992).
24. T. K. H. Chang, F. J. Gonzalez, and D. J. Waxman: Evaluation of triacetyloleandomycin, α-naphthoflavone and diethyldithiocarbamate as selective chemical probes for inhibition of human cytochromes P450. Arch. Biochem. Biophys. 311, 437-442 (1994).
25. L. Eckes and H. P. Buch: Influence of disulfiram, diethyldithiocarbamate and carbon disulfide on the metabolic formation of trifluoroacetic acid from halothane in the rat. Arzneim. Forsch. 35, 1447-1451 (1985).
26. R. C. Lind and A. J. Gandolfi: Concentration-dependent inhibition of halothane biotransformation in the guinea pig. Drug Metab. Dispos. 21, 386-389 (1993).
27. M. A. Jenner, J. L. Plummer, and M. J. Cousins: Halothane reductive metabolism in an adult surgical population. Anaesth. Intensive Care 18, 395-399 (1990).
28. F. Nomura, H. Hatano, K. Ohnishi, B. Akikusa, and K. Okuda: Effect of anticonvulsant agents on halothane-induced liver injury in human subjects and experimental animals. Hepatology 6, 952-956 (1986).
29. S. A. Wrighton and J. C. Stevens: The human hepatic cytochromes P450 involved in drug metabolism. Crit. Rev. Toxicol. 22, 1-21 (1992).
30. M. J. Cousins, J. H. Sharp, G. K. Gourlay, J. F. Adams, W. D. Haynes, and R. Whitehead: Hepatotoxicity and halothane metabolism in an animal model with application for human toxicity. Anaesth. Intensive Care 7, 9-24 (1979).
31. H. J. Ahr, L. J. King, W. Nastainczyk, and V. Ullrich: The mechanism of reductive dehalogenation of halothane by liver cytochrome P450. Biochem. Pharmacol. 31, 383-390 (1982).
32. R. A. Van Dyke, M. T. Baker, I. Jansson, and J. Schenkman: Reductive metabolism of halothane by purified cytochrome P-450. Biochem. Pharmacol. 37, 2357-2361 (1988).
33. M. Manno, S. Cazzaro, and M. Rezzadore: The mechanism of the suicidal reductive inactivation of microsomal cytochrome-P-450 by halothane. Arch. Toxicol. 65, 191-198 (1991).
34. S. Yamano, P. T. Nhamburo, T. Aoyama, U. Meyer, T. Inaba, W. Kalow, H. V. Gelboin, O. W. McBride, and F. J. Gonzalez: cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver. Biochemistry 28, 7340-7348 (1989).
35. T. Shimada, H. Yamazaki, M. Mimura, Y. Inui, and F. P. Guengerich: Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther. 270, 414-423 (1994).
36. M. Mimura, T. Baba, H. Yamazaki, S. Ohmori, Y. Inui, F. J. Gonzalez, F. P. Guengerich, and T. Shimada: Characterization of cytochrome P-450 2B6 in human liver microsomes. Drug Metab. Dispos. 21, 1048-1056 (1993).
37. M. Kawahara, S. Akita, K. Fujii, and M. Morio: Effect of calcium channel blocking agents on the reductive metabolism of halothane. J. Appl. Toxicol. 11, 29-31 (1991).