Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes

Drug Metabolism and Disposition

Volumn 25, Issue 6, 1997, Pages 740-744

  Olesen, Ole V ^a   Linnet, Kristian ^b  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

10 HYDROXYNORTRIPTYLINE; COMPLEMENTARY DNA; CYTOCHROME P450 ISOENZYME; DINORAMITRIPTYLINE; DRUG METABOLITE; NORTRIPTYLINE; TRICYCLIC ANTIDEPRESSANT AGENT; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DEMETHYLATION; DRUG ELIMINATION; DRUG HYDROXYLATION; HUMAN; HUMAN CELL; MICROSOME; PRIORITY JOURNAL;

ANTIDEPRESSIVE AGENTS, TRICYCLIC; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP1A2; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; HYDROXYLATION; ISOENZYMES; METHYLATION; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; NORTRIPTYLINE;

EID: 0030992855     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (25)

1. B. Alexanderson and O. Borgå: Urinary excretion of nortriptyline and five of its metabolites in man after single and multiple oral doses. Eur. J. Clin. Pharmacol. 5, 174-180 (1973).
2. C. Nordin, B. Siwers, J. Benitez, and L. Bertilsson: Plasma concentrations of nortriptyline and its 10-hydroxy metabolite in depressed patients: relationship to the debrisoquine hydroxylation metabolite ratio. Br. J. Clin. Pharmac. 19, 832-835 (1985).
3. L. F. Gram, K. Brøsen, P. Kragh-Sørensen, and P. Christensen: Steady-state plasma levels of E- and Z-10-OH-nortriptyline in nortriptyline-treated patients: significance of concurrent medication and the sparteine oxidation phenotype. Ther. Drug Monit. 11, 508-514 (1989).
4. M.-L. Dahl, C. Nordin, and L. Bertilsson: Enantioselective hydroxylation of nortriptyline in human liver microsomes, intestinal homogenate, and patients treated with nortriptyline. Ther. Drug Monit. 13, 189-194 (1991).
5. M.-L. Dahl, L. Bertilsson, and C. Nordin: Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: relationship to the CYP2D6 genotype. Psychopharmacology 123, 315-319 (1996)
6. L. Bertilsson and M.-L. Dahl: Polymorphic drug oxidation: relevance to the treatment of psychiatric disorders. CNS Drugs 5, 200-223 (1996).
7. R. T. Coutts, P. Su, and G. B. Baker: Involvement of CYP2D6, CYP3A4, and other cytochrome P450 isozymes in N-dealkylation reactions. J. Pharmacol. Methods 31, 177-186 (1994).
8. A. Lemoine, J. C. Gautier, D. Azoulay, L. Kiffel, C. Belloc, F. P. Guengerich, P. Maurel, P. Beaune, and J. P. Leroux: Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol. Pharmacol. 43, 827-832 (1993).
9. J. Schmider, D. J. Greenblatt, L. L. Von Moltke, J. S. Harmatz, and R. I. Shader: N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors. J. Pharmacol. Exp. Ther. 275, 592-597 (1995).
10. K. Chiba, A. Saitoh, E. Koyama, M. Tani, M. Hayashi, and T. Ishzaki: The role of S-mephenytoin 4′-hydroxylase in imipramine metabolism by human liver microsomes: a two-enzyme kinetic analysis of N-demethylation and 2-hydroxylation. Br. J. Clin. Pharmacol. 37, 237-242 (1994).
11. J. A. Goldstein, M. B. Faletto, M. Romkes-Sparks, T. Sullivan, S. Kitareewan, J. L. Raucy, J. M. Lasker, and B. I. Ghanayem: Evidence that CYP2C19 is the major (S)-mephenytoin 4′-hydroxylase in humans. Biochem. 33, 1743-1752 (1994).
12. H. H. Riem, J. Chen, A. U. Freiburghaus, and F. Follath: Metabolism of theophylline by cDNA-expressed human cytochromes P-450. Br. J. Clin. Pharmacol. 39, 321-326 (1995).
13. U. Fuhr, J. Doehmer, N. Battula, C. Wölfer, C. Kudla, Y. Keita, and A. H. Staib: Biotransformation of caffeine and theophylline in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. Biochem. Pharmacol. 43, 225-235 (1992).
14. S. D. Hall, F. P. Guengerich, R. A. Branch, and G. R. Wilkinson: Characterization and inhibition of mephenytoin 4-hydroxylase activity in human liver microsomes. J. Pharmacol. Exp. Ther. 240, 216-222 (1987).
15. T. Shimada, Y. Yamazaki, M. Mimura, Y. Inui, and F. P. Guengerich: Interindividual variations in human liver cytochrome P450 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).
16. J. A. Goldstein, and S. M. de Morais: Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 4, 285-299 (1994).
17. R. C. Baselt and R. H. Cravey (eds.). Nortriptyline. In: "Disposition of Toxic Drugs and Chemicals in Man," pp. 562-564. Chemical Toxicology Institute, Foster City, CA, (1995).
18. Task Force on the Use of Laboratory Tests in Psychiatry: Tricyclic antidepressant - blood level measurements and clinical outcome: an APA Task Force Report. Am. J. Psychiatry 142, 155-162 (1985).
19. P. Su, R. T. Coutts, G. B. Baker, and M. Daneshtalab: Analysis of imipramine and three metabolites produced by isozyme CYP2D6 expressed in a human cell line. Xenobiotica 23, 1289-1298 (1993).
20. M. Jerling and G. Alván: Nonlinear kinetics of nortriptyline in relation to nortriptyline clearance as observed during therapeutic drug monitoring. Eur. J. Clin. Pharmacol. 46, 67-70 (1994).
21. E. Skjelbo, K. Brøsen, J. Hallas, and L. F. Gram: The mephenytoin oxidation polymorphism is partially responsible for the N-demethylation of imipramine. Clin. Pharmacol. Ther. 49, 18-23 (1991).
22. E. Koyama, T. Tanaka, K. Chiba, S. Kawakatsu, S., Morinobu, S. Totsuka, and T. Ishizaki: Steady-state plasma concentrations of imipramine and desipramine in relation to S-mephenytoin 4′-hydroxylation status in Japanese depressive patients. J. Clin. Psychopharmacol. 16, 286-293 (1996).
23. J. Schmider, D. J. Greenblatt, L. L. von Moltke, and R. I. Shader: Relationship of in vitro data on drug metabolism to in vivo pharmacokinetics and drug interactions: implications for diazepam disposition in humans. J. Clin. Psychopharmacol. 16, 267-272 (1996).
24. K. G. Jensen, H. E. Poulsen, J. Doehmer, and S. Loft: Kinetics and inhibition by fluvoxamine of phenacetin O-deethylation in V79 cells expressing human CYP1A2. Pharmacol. Toxicol. 76, 286-288 (1995).
25. R. T. Coutts, O. O. Bolaji, P. Su, and G. B. Baker: Metabolism of methoxyphenamine in vitro by a CYP2D6 microsomal preparation. Drug Metab. Dispos. 22, 756-760 (1994).