Evidence for CYP2D1-mediated primary and secondary O-dealkylation of ethylmorphine and codeine in rat liver microsomes

Biochemical Pharmacology

Volumn 53, Issue 4, 1997, Pages 603-609

  Xu, Bang Qian ^a   Aasmundstad, Tor A ^a   Christophersen, Asbjørg S ^a   Mørland, Jørg ^a   Bjørneboe, Anders ^a  

^a Natl Inst of Forensic Toxicology   (Norway)

Author keywords

codeine, ethylmorphine; CYP2D1; norcodeine; norethylmorphine; O dealkylation

Indexed keywords

CODEINE; CYTOCHROME P450 ISOENZYME; ETHYLMORPHINE;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIVER METABOLISM; LIVER MICROSOME; NONHUMAN; PRIORITY JOURNAL; RABBIT; ULTRAVIOLET SPECTROPHOTOMETRY;

ANIMALS; CODEINE; CYTOCHROME P-450 CYP2D6; DEALKYLATION; ETHYLMORPHINE; FEMALE; MALE; MICROSOMES, LIVER; NARCOTICS; RABBITS; RATS; RATS, WISTAR;

EID: 0031581854     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(96)00736-8     Document Type: Article

References (25)

1. 1. Rane A, Modiri AR and Gerdin E, Ethylmorphine O-deethylation cosegregates with the debrisoquine genetic metabolic polymorphism. Clin Pharmacol Ther 52: 257-264, 1992.
2. 2. Gonzalez FJ, Skoda RC, Kimura S, Umeno M, Zanger UM, Nebert DW, Gelboin HV Hardwick JP and Meyer UA, Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature 331: 442-446, 1988.
3. 3. Neville CF, Ninomiya S, Shimada N, Kamataki T, Imaoka S and Funae Y, Characterization of specific cytochrome P450 enzymes responsible for the metabolism of diazepam in hepatic microsomes of adult male rats. Biochem Pharmacol 45: 59-65, 1993.
4. 4. Zanger UM, Vilbois F, Hardwick JP and Meyer UA, Absence of hepatic cytochrome P450bufl causes genetically deficient debrisoquine oxidation in man. Biochemistry 27: 5447-5454, 1988.
5. 5. Nebert DW, Nelson DR, Adsenik M, Coon MJ, Estabrook RW, Gonzalez FJ, Guengerich FP, Gunsalus IC, Johnson EF, Kemper B, Levin W, Phillips JR, Sato R and Waterman MR, The P450 superfamily: update listing of all genes and recommended nomenclature for the chromosomal loci. DNA 8: 1-13, 1989.
6. 6. Matsunaga E, Zanger UM, Hardwick JP, Gelboin HV, Meyer UA and Gonzalez FJ, The CYP2D gene subfamily: analysis of the molecular basis of the debrisoquine 4-hydroxylase deficiency in DA rats. Biochemistry 28: 7349-7355, 1989.
7. 7. Xu BQ, Bugge A, Gunderson H, Malterud KE and Christophersen AS, Synthesis and spectroscopic studies of norethylmorphine. J Pharm Biomed Analy 10: 303-307, 1992.
8. 8. Gadeholt G, Aarbakke J, Dybing E, Sjöblom M and Mørland J, Hepatic microsomal drug metabolism, glutamyl transferase activity and in vitro antipyrine half-life in rats chronically fed an ethanol diet, a control diet and a chow diet. J Pharmacol Exp Ther 213: 196-203, 1980.
9. 9. Aasmundstad TA, Ripel Å, Bodd E, Bjørneboe A and Mørland J, Different biotransformation of morphine in isolated liver cells from guinea pig and rat. Biochem Pharmacol 46: 961-968, 1993.
10. 10. Lowry OH, Rosebrough AL, Farr AL and Randell RJ, Protein measurement with Folin phenol reagent. J Biol Chem 93: 265-275, 1951.
11. 11. Mikus G, Somogyi AA, Bochner F and Eichelbaum M, Codeine O-demethylation: rat strain differences and the effects of inhibitors. Biochem Pharmacol 41: 757-762, 1991.
12. 12. Xu BQ, Aasmundstad TA, Bjørneboe A, Christophersen AS and Mørland J, Ethylmorphine O-deethylation in isolated rat hepatocytes: Involvement of codeine O-demethylation enzyme systems. Biochem Pharmacol 49: 453-460, 1995.
13. 13. Kobayashi S, Murray S, Watson D, Sesardic D, Davies DS and Boobis AR, The specificity of inhibition of debrisoquine 4-hydroxylase activity by quinidine and quinine in the rat is the inverse of that in man. Biochem Pharmacol 38: 2795-2799, 1989.
14. 14. Smith DA, Species differences in metabolism and pharmacokinetics: Are we close to an understanding? Drug Metab Rev 23: 355-373, 1991.
15. 15. Siddoway LA, Thompson KA, McAllister CB, Wang T, Wilkinson GR, Roden DM and Woosley RL, Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation 75: 785-791, 1987.
16. 16. Xu BQ, Bjørneboe A, Ripel Å, Aasmundstad TA, Christophersen AS and Mørland J, Ethylmorphine metabolism in isolated rat hepatocytes, Pharmacol Toxicol 73: 35-40, 1993.
17. 17. Bodd E, Christophersen AS and Fongen U, Normorphine is the major metabolite of norcodeine in isolated rat hepatocytes. Acta Pharmacol et Toxicol 59: 252-253, 1986.
18. 18. Aasmundstad TA, Xu BQ, Johansson I, Ripel Å, Bjørneboe A, Christophersen AS, Bodd E and Mørland J, Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose. Br J Clin Pharmacol 39: 611-620, 1995.
19. 19. Yue QY, Svensson JO, Alm C, Sjöqvist F and Säwe J, Interindividual and interethnic differences in the demethylation and glucuronidation of codeine. Br J Clin Pharmacol 28: 629-637, 1989.
20. 20. Rane A and Ask B, A conspicuous down-regulating effect of morphine on essential steroid hydroxylation reactions and certain drug N-demethylations. J Steroid Biochem Mol Biol 41: 91-98, 1992.
21. 21. Newton DJ, Wang RW and Lu AYH, Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23: 154-158, 1995.
22. 22. Back DJ, Tjia JF, Karbwang Y and Colbert J, In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinolines. Br J Clin Pharmacol 26: 23-29, 1988.
23. 23. Brøsen K, Zeugin T and Meyer UA, Role of P450IID6, the target of the sparteine-debrisoquine oxidation polymorphism, in the metabolism of imipramine. Clin Pharmacol Ther 49: 609-617, 1991.
24. 24. Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV and Miners JO, Specificity of substrate and inhibitor probes for human cytochrome P450 1A1 and 1A2. J Pharmacol Exp Ther 265: 401-407, 1993.
25. 25. Tassaneeyakul W, Veronese ME, Birkett DJ, Gonzalez FJ and Miners JO, Validation of 4-nitrophenol as an in vitro substrate probe for human liver CYP2E1 using cDNA expression and microsomal kinetic techniques. Biochem Pharmacol 46: 1975-1981, 1993.