Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: Relationship to the CYP2D6 genotype

Psychopharmacology

Volumn 123, Issue 4, 1996, Pages 315-319

  Dahl, Marja Liisa ^a   Bertilsson, Leif ^a   Nordin, Conny ^a,b  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^b LINKÖPING UNIVERSITY HOSPITAL   (Sweden)

Author keywords

10 Hydroxynortriptyline; CYP2D6 genotype; CYP2D6 phenotype; Debrisoquine; Genetic polymorphism; Nortriptyline

Indexed keywords

10 HYDROXYNORTRIPTYLINE; 4 HYDROXYDEBRISOQUINE; CYTOCHROME P450 ISOENZYME; DEBRISOQUINE; DRUG METABOLITE; NORTRIPTYLINE;

ADULT; ALLELE; ARTICLE; CAUCASIAN; CLINICAL ARTICLE; CLINICAL TRIAL; DEPRESSION; DRUG BLOOD LEVEL; DRUG METABOLISM; FEMALE; FOLLOW UP; GENDER; GENE AMPLIFICATION; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; MALE; PHENOTYPE; POLYMERASE CHAIN REACTION; PREDICTION; PRIORITY JOURNAL; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; STEADY STATE;

ADULT; AGED; ALLELES; ANTIDEPRESSIVE AGENTS, TRICYCLIC; CYTOCHROME P-450 CYP2D6; DEBRISOQUIN; FEMALE; FOLLOW-UP STUDIES; GENOTYPE; HUMANS; MALE; MIDDLE AGED; NORTRIPTYLINE; POLYMERASE CHAIN REACTION; REGRESSION ANALYSIS;

EID: 0029926315     PISSN: 00333158     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF02246640     Document Type: Article

References (35)

1. Alexanderson B, Borgå O (1973) Urinary excretion of nortriptyline and live of its metabolites in man after single and multiple oral doses. Eur J Clin Pharmacol 5:174-180
2. Alexanderson B, Evans DAP, Sjöqvist F (1969) Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy. BMJ 4:764-768
3. Alexanderson B, Borgå O, Alván G (1973) The availability of orally administered nortriptyline. Eur J Clin Pharmacol 5:181-185
4. Asberg M, Evans DAP, Sjöqvist F (1971a) Genetic control of nortriptyline kinetics in man. A study of relatives of propositi with high plasma concentrations. J Med Genet 8:129-135
5. Åsberg M, Cronholm B, Sjöqvist F, Tuck D (1971b) Relationship between plasma level and therapeutic effect of nortriptyline. BMJ 3:331-334
6. Bertilsson L, Eichelbaum M, Mellström B, Säwe J, Schulz H-U, Sjöqvist F (1980) Nortriptyline and antipyrine clearance in relation to debrisoquine hydroxylation in man. Life Sci 27:1673-1677
7. Bertilsson L, Mellström B, Sjöqvist F, Mårtensson B, Åsberg M (1981) Slow hydroxylation of nortriptyline and concomitant poor debrisoquine hydroxylation: clinical implications. Lancet i: 560-561
8. Bertilsson L, Åsberg-Wistedt A, Gustafsson LL, Nordin C (1985) Extremely rapid hydroxylation of debrisoquine: a case report with implication for treatment with nortriptyline and other tricyclic antidepressants. Ther Drug Monit 7:478-480
9. Bertilsson L, Dahl M-L, Sjöqvist F, Åberg-Wistedt A, Humble M, Johansson I, Lundqvist E, Ingelman-Sundberg M (1993) Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine. Lancet 341:63
10. Borgå O, Palmér L, Sjöqvist F, Holmstedt B (1973) Mass fragmentography used in quantitative analysis of drugs and endogenous compounds in biological fluids. In: Pharmacology and the future of man. Proceedings of the 5th International Congress on Pharmacology, vol. III. S. Karger AG, Basel, pp 56-68
11. Breyer-Pfaff U, Pfandl B, Nill K, Nusser E, Monney C, Jonzier-Perey M, Baettig D, Buumann P (1992) Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. Clin Pharmacol Ther 52:350-358
12. Broly F, Gaedigk A, Heim M, Eichelbaum M, Morike K, Meyer UA (1991) Debrisoquine/sparteine hydroxylation genotype and phenotype: analysis of common mutations and alleles of CYP2D6 in a European population. DNA Cell Biol 10:545-558
13. Brøsen K, Nielsen PN, Brusgaard K, Gram LF, Skjødt K (1994) CYP2D6 genotype determination in the Danish population. Eur J Clin Pharmacol 47:221-225
14. Dahl M-L, Johansson I, Porsmyr Palmertz M, Ingelman-Sundberg M, Sjöqvist F (1992) Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population. Clin Pharmacol Ther 51:12-17
15. Dahl M-L, Johansson I, Bertilsson L, Ingelman-Sundberg M, Sjöqvist F (1995) Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis. J Pharmacol Exp Ther 274:516-520
16. Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ (1979) Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16:183-187
17. 1795 in exon 3 generates a premature stop codon. Pharmacogenetics 4:271-274
18. Evert B, Griese E-U, Eichelbaum M (1994b) A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine 324 to proline exchange is associated with the poor metabolizer phenotype of sparteine. Naunyn Schmiedeberg's Arch Pharmacol 350:434-439
19. Gaedigk A, Blum M, Gaedigk R, Eichelbaum M, Meyer UA (1991) Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet 48:943-950
20. Gram LF (1977) Plasma level monitoring of tricyclic antidepressant therapy. Clin Pharmacokinet 2:237-251
21. Gram LF, Brøsen K, Kragh-Sørensen P, Christensen P (1989) 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
22. Hammer W, Sjöqvist F (1967) Plasma level of monomethylated antidepressants during treatment with imipramine-like compounds. Life Sci 6:1895-1903
23. Harris RZ, Benet LZ, Schwartz JB (1995) Gender effects in pharmacokinetics and pharmacodynamics. Drugs 50:222-239
24. Heim M, Meyer UA (1990) Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification. Lancet 336:529-532
25. Jerling M, Merlé Y, Mentré F, Mallet A (1994) Population pharmacokinetics of nortriptyline during monotherapy and during concomitant treatment with drugs that inhibit CYP2D6 an evaluation with the nonparametric maximum likelihood method. Br J Clin Pharmacol 38:453-462
26. Johansson I, Lundqvist E, Bertilsson L, Dahl M-L, Sjöqvist F, Ingelman-Sundberg M (1993) Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc Natl Acad Sci USA 90:11825-11829
27. Mahgoub A, Dring LG, Idle JR, Lancaster R, Smith RL (1977) Polymorphic hydroxylation of debrisoquine in man. Lancet ii: 584-586
28. Mellström B, Bertilsson L, Säwe J, Schulz H-U, Sjöqvist F (1981) E- and Z-10-hydroxylation of nortriptyline: relationship to polymorphic debrisoquine hydroxylation. Clin Pharmacol Ther 30:189-193
29. Nordin C, Siwers B, Benitez J, Bertilsson L (1985a) Plasma concentrations of nortriptyline and its 10-hydroxy metabolite in depressed patients relationship to the debrisoquine hydroxylation metabolic ratio. Br J Clin Pharmacol 19:832-835
30. Nordin C, Bertilsson L, Siwers B (1985b) CSF and plasma levels of nortriptyline and its 10-hydroxy metabolite. Br J Clin Pharmacol 20:411-413
31. Nordin C, Bertilsson L, Siwers B (1987) Clinical and biochemical effects during treatment of depression with nortriptyline: the role of 10-hydroxynortriptyline. Clin Pharmacol Ther 42: 10-19
32. Nordin C, Bertilsson L, Dahl M-L, Resul B, Toresson G, Sjöqvist F (1991) Treatment of depression with E-10-hydroxynortriptyline - a pilot study on biochemical effects and pharmacokinetics. Psychopharmacology 103:287-290
33. Prescorn SH, Jerkovich GS (1990) Central nervous system toxicity of tricyclic antidepressants: pharmacology, course, risk factors and role of therapeutic drug monitoring. J Clin Psychopharmacol 10:88-95
34. Tucker GT, Silas JH, Iyun AO, Lennard MS, Smith AJ (1977) Polymorphic hydroxylation of debrisoquine. Lancet ii:718
35. Young RC, Alexopoulos GS, Shamoian CA, Dhar AK, Kutt H (1984) Plasma 10-hydroxynortriptyline in elderly depressed patients. Clin Pharmacol Ther 35:540-544