Serum clomipramine and desmethylclomipramine levels in a CYP2C19 and CYP2D6 intermediate metabolizer

Pharmacogenomics. 2017 May;18(7):601-605. doi: 10.2217/pgs-2017-0015. Epub 2017 May 4.

Abstract

Pharmacogenetics within psychiatry has the potential to aid in the dose and selection of medications. A substantial number of psychiatric medications are metabolized through either of the highly polymorphic drug-metabolizing enzymes CYP2D6 and CYP2C19. Of these, clomipramine is subject to metabolism by both CYP2C19 and CYP2D6, leaving individuals with deficiencies of these drug-metabolizing enzymes at risk of higher concentrations of the parent molecule. Herein, we present the case of a 29-year-old male with diagnoses of depression and obsessive compulsive disorder who had trialed and failed a dozen psychiatric medications, many of which are subject to metabolism by CYP2D6 and/or CYP2C19, and had most recently been taking clomipramine for approximately 2.5 years. Pharmacogenetic testing revealed this patient to be an intermediate metabolizer for both CYP2C19 (*1/*2) and CYP2D6 (*4/*41), which resulted in considerably elevated serum trough concentrations of clomipramine and its active metabolite desmethylclomipramine. This case provides a retrospective view of how the knowledge of an individual's pharmacogenetic test results can aid in their clinical care.

Keywords: CYP2C19; CYP2D6; clomipramine; desmethylclomipramine; pharmacogenetics; pharmacogenomics.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Antidepressive Agents, Tricyclic / blood
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Clomipramine / analogs & derivatives*
  • Clomipramine / blood*
  • Clomipramine / therapeutic use
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 CYP2C19 / metabolism*
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Depressive Disorder / blood
  • Depressive Disorder / drug therapy
  • Depressive Disorder / genetics
  • Humans
  • Male
  • Obsessive-Compulsive Disorder / blood
  • Obsessive-Compulsive Disorder / drug therapy
  • Obsessive-Compulsive Disorder / genetics
  • Retrospective Studies

Substances

  • Antidepressive Agents, Tricyclic
  • desmethylclomipramine
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6
  • Clomipramine