, Volume 123, Issue 4, pp 315–319

Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: relationship to theCYP2D6 genotype

  • M. -L. Dahl
  • L. Bertilsson
  • C. Nordin
Original Investigation

DOI: 10.1007/BF02246640

Cite this article as:
Dahl, M.L., Bertilsson, L. & Nordin, C. Psychopharmacology (1996) 123: 315. doi:10.1007/BF02246640


The relationship between theCYP2D6 genotype and the steady state plasma levels of nortriptyline (NT), its main active metabolite 10-hydroxynortriptyline (10-OH-NT) and the NT/10-OH-NT ratio were studied in 21 Caucasian depressed patients treated with 100–150 mg NT daily. The patients had participated in a previously published study investigating the role of NT and 10-OH-NT for the therapeutic effect of NT, and the plasma level data were from that study. In the present follow-up study, the patients were genotyped with respect to the polymorphicCYP2D6 by allelespecific PCR amplification andEcoRIRFLP. One poor metabolizer (PM) was identified and she had the highest plasma concentration of NT. Among the 20 extensive metabolizers (EM), the genotype (homozygous versus heterozygous EM) alone was not found to explain the variance in dose-corrected NT concentrations, but contributed significantly when gender was also taken into account. Together, these factors accounted for 59% of the variability in NT levels. Female patients had higher plasma levels of NT than male patients. 10-OH-NT levels were influenced by genotype, and NT/10-OH-NT ratio by genotype and gender. The present follow-up study confirms a relationship between theCYP2D6 genotype and the plasma levels of NT and its active metabolite. Identification of PM by genotyping should be of value for the prediction of the plasma levels and, consequently, the lower than average dose of NT required for optimal therapy. Also among EM, the genotype contributes to the variability in NT and 10-OH-NT levels but alone is of limited practical value for the prediction of optimal dosage.

Key words

Nortriptyline 10-Hydroxynortriptyline CYP2D6 phenotype CYP2D6 genotype Debrisoquine Genetic polymorphism 

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • M. -L. Dahl
    • 1
  • L. Bertilsson
    • 1
  • C. Nordin
    • 2
    • 3
  1. 1.Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska InstitutetHuddinge University HospitalHuddingeSweden
  2. 2.Department of Clinical Neuroscience and Family Medicine, Division of Psychiatry, Karolinska Institutet, HuddingeUniversity HospitalHuddingeSweden
  3. 3.Department of PsychiatryUniversity HospitalLinköpingSweden

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