Human halothane reduction in vitro by cytochrome P450 2A6 and 3A4: Identification of low and high K(M) isoforms

Drug Metabolism and Disposition

Volumn 26, Issue 6, 1998, Pages 605-607

  Spracklin, Douglas K ^b   Kharasch, Evan D ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 2A6; CYTOCHROME P450 3A4; CYTOCHROME P450 ISOENZYME; HALOTHANE; METHOXSALEN; TROLEANDOMYCIN; UNCLASSIFIED DRUG;

ARTICLE; DRUG ABSORPTION; DRUG METABOLISM; DRUG TRANSFORMATION; ENZYME KINETICS; HUMAN; LIVER METABOLISM; LIVER TOXICITY; PRIORITY JOURNAL;

ANESTHETICS, INHALATION; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 ENZYME SYSTEM; HALOTHANE; HUMANS; ISOENZYMES; LUNG; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; OXIDATION-REDUCTION;

EID: 0031765699     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (30)

1. Ahr HJ, King LJ, Nastainczyk W and Ullrich V (1982) The mechanism of reductive dehalogenation of halothane by liver cytochrome P450. Biochem Pharmacol 31:383-390.
2. Akita S, Kawahara M, Takeshita T, Morio M and Fujii K (1989) Halothane-induced hepatic microsomal lipid peroxidation in guinea pigs and rats. J Appl Toxicol 9:9-14.
3. 2-isoprostanes. Anesthesiology 84:910-916.
4. Baker MT, Vasquez MT and Chiang C-K (1991) 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.
5. Bourdi M, Chen W, Peter RM, Martin JL, Buters JTM, Nelson SD and Pohl LR (1996) Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chem Res Toxicol 9:1159-1166.
6. Carpenter RL, Eger EI II, Johnson BH, Unadkal JD and Sheiner LB (1986) The extent of metabolism of inhaled anesthetics in humans. Anesthesiology 65:201-205.
7. Christ DD, Kenna JG, Kammerer W, Satoh H and Pohl LR (1988a) Enflurane metabolism produces covalently bound liver adducts recognized by antibodies from patients with halothane hepatitis. Anesthesiology 69:833-838.
8. Christ DD, Satoh H, Kenna JG and Pohl LR (1988b) Potential metabolic basis for enflurane hepatitis and the apparent cross-sensitization between enflurane and halothane. Drug Metab Dispos 16:135-140.
9. Cousins MJ, Gourlay GK, Knights KM, Hall PM, Lunam CA and O'Brien P (1987) A randomized prospective controlled study of the metabolism and hepatotoxicity of halothane in humans. Anesth Analg 66:299-308.
10. Cousins MJ, Plummer JL and Hall PM (1989) Risk factors for halothane hepatitis. Aust NZ J Surg 59:5-14.
11. de Groot H and Noll T (1983) Halothane hepatotoxicity: Relation between metabolic activation, hypoxia, covalent binding, lipid peroxidation and liver cell damage. Hepatology 3:601-606.
12. Gut J, Christen U, Frey N, Koch V and Stoffler D (1995) Molecular mimicry in halothane hepatitis: Biochemical and structural characterization of lipoylated autoantigens. Toxicology 97:199-224.
13. Gut J, Christen U and Huwyler J (1993) Mechanisms of halothane toxicity: Novel insights. Pharmacol Ther 58:133-155.
14. Jenner MA, Plummer JL and Cousins MJ (1990) Halothane reductive metabolism in an adult surgical population. Anaesth Intensive Care 18:395-399.
15. Kenna JG, Martin JL, Satoh H and Pohl LR (1990) Factors affecting the expression of trifluoroacetylated liver microsomal protein neoantigens in rats treated with halothane. Drug Metab Dispos 18:788-793.
16. Kenna JG, Neuberger J and Williams R (1988) Evidence for expression in human liver of halothane-induced neoantigens by antibodies in sera from patients with halothane hepatitis. Hepatology 8:1635-1641.
17. Kharasch ED, Hankins D, Mautz D and Thummel KE (1996) Identification of the enzyme responsible for oxidative halothane metabolism: Implications for prevention of halothane hepatitis. Lancet 347:1367-1371.
18. 14C]halothane to human liver microsomes: A role for cytochrome P4502E1 at low substrate concentrations. Drug Metab Dispos 24:1307-1313.
19. Maenpaa J, Juvonen R, Raunio H, Rautio A and Pelkonen O (1994) Metabolic interactions of methoxsalen and coumarin in humans and mice. Biochem Pharmacol 48:1363-1369.
20. Manno M, Ferrara R, Cazzaro S, Rigotti P and Ancona E (1992) Suicidal inactivation of human cytochrome P-450 by carbon tetrachloride and halothane in vitro. Pharmacol Toxicol 70:13-18.
21. Muller R and Srier A (1982) Modification of liver microsomal lipids by halothane metabolites: A multi nuclear NMR spectroscopic study. Naunyn Schmiedebergs Arch Pharmacol 321:234-237.
22. Newton DJ, Wang RW and Lu AYH (1995) Cytochrome P450 inhibitors: Evaluations of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23:154-158.
23. Nomura F, Hatano H, Ohnishi K, Akikusa B and Okuda K (1986) Effect of anticonvulsant agents on halothane-induced liver injury in human subjects and experimental animals. Hepatology 6:952-956.
24. Pohl LR, Kenna JG, Satoh H, Christ DD and Martin JL (1989) Neoantigens associated with halothane-hepatitis. Drug Metab Rev 20:203-217.
25. Ray DC and Drummond GB (1991) Halothane hepatitis. Br J Anaesth 67:84-99.
26. Sato N, Fujii K, Yuge O and Mono M (1990) 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.
27. Spracklin D, Hankins DC, Fisher JM, Thummel KE and Kharasch ED (1997) Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism. J Pharmacol Exp Ther 281:400-411.
28. Spracklin D, Thummel KE and Kharasch ED (1996) Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4. Drug Metab Dispos 24:976-983.
29. Wark H, Earl J, Chau DD and Overton J (1990) Halothane metabolism in children. Br J Anaesth 64:474-481.
30. Wrighton SA and Stevens JC (1992) The human hepatic cytochromes P450 involved in drug metabolism. Crit Rev Toxicol 22:1-21.