The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population

British Journal of Clinical Pharmacology

Volumn 65, Issue 1, 2008, Pages 134-138

  Halling, Jónrit ^a,c   Weihe, Pál ^b   Brosen, Kim ^a  

^a UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^b FAROESE HOSPITAL SYSTEM   (Faroe Islands)

^c UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

Amitriptyline; CYP2D6 polymorphism; Faroe Islands; Nortriptyline; The Faroese population

Indexed keywords

AMITRIPTYLINE; CYTOCHROME P450 2D6; DRUG METABOLITE; NORTRIPTYLINE; SPARTEINE;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CONFIDENCE INTERVAL; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG BLOOD LEVEL; DRUG METABOLISM; ENZYME ACTIVITY; FEMALE; GENOTYPE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MALE; PHENOTYPE; PRIORITY JOURNAL;

ADULT; AGED; AGED, 80 AND OVER; AMITRIPTYLINE; ANTIDEPRESSIVE AGENTS, TRICYCLIC; CYTOCHROME P-450 CYP2D6; DENMARK; FEMALE; HUMANS; MALE; MIDDLE AGED; NORTRIPTYLINE; POLYMORPHISM, GENETIC;

EID: 37249083501     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2007.02969.x     Document Type: Article

References (27)

1. Barbui C, Hotopf M. Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials. Br J Psychiatry 2001 178 : 129 44.
2. Brosen K. Some aspects of genetic polymorphism in the biotransformation of antidepressants. Therapie 2004 59 : 5 12.
3. Alván G, Becthel P, Islius L, Gundert-Remy U. Hydrolylation polymorphisms of debrisoquine and mephenytoin in European population. Eur J Clin Pharmacol 1990 39 : 533 7.
4. Halling J, Petersen MS, Damkier P, Nielsen F, Grandjean P. Weihe P, Lundgren S, Lundblad MS, Brosen K. Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population. Eur J Clin Pharmacol 2005 61 : 491 7.
5. Santer R, Kinner M, Steuerwald U, Kjaergaard S, Skovby F, Simonsen H, Shaiu W-L, Chen T-T, Schneppenheim R, Schaub J. Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands. Eur J Hum Gen 2001 9 : 388 91.
6. Schwartz M, Sorensen N, Brandt NJ, Hogdall E, Holm T. High incidence of cystic fibrosis on the Faroe Islands: a molecular and genealogical study. Hum Genet 1995 95 : 703 6.
7. Breyer-Pfaff U. The metabolic fate of amitriptyline, nortriptyline and amitriptylinoxide in man. Drug Metab Rev 2004 36 : 723 46.
8. Mellstrom B, Bertilsson L, Sawe J, Schulz HU, Sjoqvist F. E- and Z-10-hydroxylation of nortriptyline: relationship to polymorphic debrisoquine hydroxylation. Clin Pharmacol Ther 1981 30 : 189 93.
9. Balant-Gorgia AE, Schulz P, Dayer P, Balant L, Kubli A, Gertsch C, Garrone G. Role of oxidation polymorphism on blood and urine concentrations of amitriptyline and its metabolites in man. Arch Psychiatr Nervenkr 1982 232 : 215 22.
10. Nordin C, Bertilsson L. Active hydroxymetabolites of antidepressants. Emphasis on E-10-hydroxy-nortriptyline. Clin Pharmacokinet 1995 28 : 26 40.
11. Breyer-Pfaff U, Pfandl B, Nill K, Nusser E, Monney C, Jonzier-Perey M, Baettig D, Baumann P. Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. Clin Pharmacol Ther 1992 52 : 350 8.
12. Bertilsson L, Alexanderson B. Stereospecific hydroxylation of nortriptyline in man in relation to interindividual differences in its steady-state plasma level. Eur J Clin Pharmacol 1972 4 : 201 5.
13. Gram LF, Brosen K, Kragh-Sorensen P, Christensen P. 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 1989 11 : 508 14.
14. Nilvebrant L, Nordin C. Affinity of nortriptyline and its E-10-hydroxy metabolite for muscarinic receptors. Pharmacol Toxicol 1991 68 : 64 7.
15. Nordin C, Krijzer F. Antidepressant and anxiolytic profiles of E-10-hydroxynortriptyline on electrocorticograms of rats. Neuropsychobiology 1996 34 : 44 8.
16. Bertilsson L, Mellstrom B, Sjoqvist F. Pronounced inhibition of noradrenaline uptake by 10-hydroxymetabolites of nortriptyline. Life Sci 1979 25 : 1285 92.
17. Dahl ML, Nordin C, Bertilsson L. Enantioselective hydroxylation of nortriptyline in human liver microsomes, intestinal homogenate, and patients treated with nortriptyline. Ther Drug Monit 1991 13 : 189 94.
18. Dahl-Puustinen ML, Perry TL Jr, Dumont E, von Bahr C, Nordin C, Bertilsson L. Stereoselective disposition of racemic E-10-hydroxynortriptyline in human beings. Clin Pharmacol Ther 1989 45 : 650 6.
19. Nordin C, Siwers B, Benitez J, Bertilsson L. Plasma concentrations of nortriptyline and its 10-hydroxy metabolite in depressed patients relationship to the debrisoquine hydroxylation metabolic ratio. Br J Clin Pharmacol 1985 19 : 832 5.
20. Dahl ML, Bertilsson L, Nordin C. Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: relationship to the CYP2D6 genotype. Psychopharmacol (Berl) 1996 123 : 315 9.
21. Vinks A, Inaba T, Otton SV, Kalow W. Sparteine metabolism in Canadian Causcasians. Clin Pharmacol Ther 1982 31 : 23 9.
22. Brosen K, Otton SV, Gram LF. Sparteine oxidation polymorphism in Denmark. Acta Pharmacol Toxicol 1985 57 : 357 60.
23. Nielsen KK, Brosen K. High-performance liquid chromatography of clomipramine and metabolites in human plasma and urine. Ther Drug Monit 1993 15 : 122 8.
24. Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Gerlach M, Kuss HJ, Laux G, Muller-Oerlinghausen B, Rao ML, Riederer P, Zernig G. Arbeitsge-meinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie - Therapeutic Drug Monitoring Group. Pharmacopsychiatry 2004 37 : 243 65.
25. Kaneko A, Lum JK, Yaviong L, Takahashi N, Ishizaki T, Bertilsson L, Kobayakawa T, Bjorkman A. High variable frequencies of CYP2C19 mutations: medical consequences of poor drug metabolism in Vanuatu and other Pacific islands. Pharmacogenetics 1999 9 : 581 90.
26. Steimer W, Müller B, Leucht S, Kissling W. Pharmacogenetics: a new diagnostic tool in the management of antidepressive drug therapy. Clin Chim Acta 2001 308 : 33 41.
27. Rosholm JU, Hallas J, Gram LF. Outpatient utilization of antidepressants: a prescription database analysis. J Affect Disord 1993 27 : 21 8.