Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine

Donald E. McAlpine, Joanna M Biernacka, David A. Mrazek, Dennis J. O'Kane, Susanna R. Stevens, Loralie J. Langman, Vicki L. Courson, Jyoti Bhagia, Thomas P. Moyer

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

This study examines the relationship between blood concentrations of venlafaxine and its active metabolite, O-desmethyl venlafaxine (ODV), and genetic variants of the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human subjects. Trough blood concentrations were measured at steady state in patients treated with venlafaxine extended release in a clinical practice setting. CYP2D6 and CYP2C19 genotypes were converted to activity scores based on known activity levels of the two alleles comprising a genotype. After adjusting for drug dose and gender effects, higher CYP2D6 and CYP2C19 activity scores were significantly associated with lower venlafaxine concentrations (P < 0.001 for each). Only CYP2D6 was associated with the concentration of ODV (P < 0.001), in which genotypes with more active alleles were associated with higher ODV concentrations. The sum of venlafaxine plus ODV concentration showed the same pattern as venlafaxine concentrations with CYP2D6 and CYP2C19 genotypes with higher activity scores being associated with a lower venlafaxine plus ODV concentration (2D6 P = 0.01; 2C19 P < 0.001). Because allelic variants in both CYP2D6 and CYP2C19 influence the total concentration of the active compounds venlafaxine and ODV, both CYP2D6 and CYP2C19 genotypes should be considered when using pharmacogenomic information for venlafaxine dose alterations.

Original languageEnglish (US)
Pages (from-to)14-20
Number of pages7
JournalTherapeutic Drug Monitoring
Volume33
Issue number1
DOIs
StatePublished - Feb 2011

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Cytochrome P-450 Enzyme System
Pharmacokinetics
Cytochrome P-450 CYP2D6
Genotype
Venlafaxine Hydrochloride
Alleles
Pharmacogenetics
Cytochrome P-450 CYP2C19

Keywords

  • CYP2C19
  • CYP2D6
  • genotype
  • O-desmethyl venlafaxine
  • poor metabolizer

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

McAlpine, D. E., Biernacka, J. M., Mrazek, D. A., O&apos;Kane, D. J., Stevens, S. R., Langman, L. J., ... Moyer, T. P. (2011). Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine. Therapeutic Drug Monitoring, 33(1), 14-20. https://doi.org/10.1097/FTD.0b013e3181fcf94d

Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine. / McAlpine, Donald E.; Biernacka, Joanna M; Mrazek, David A.; O&apos;Kane, Dennis J.; Stevens, Susanna R.; Langman, Loralie J.; Courson, Vicki L.; Bhagia, Jyoti; Moyer, Thomas P.

In: Therapeutic Drug Monitoring, Vol. 33, No. 1, 02.2011, p. 14-20.

Research output: Contribution to journalArticle

McAlpine, DE, Biernacka, JM, Mrazek, DA, O&apos;Kane, DJ, Stevens, SR, Langman, LJ, Courson, VL, Bhagia, J & Moyer, TP 2011, 'Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine', Therapeutic Drug Monitoring, vol. 33, no. 1, pp. 14-20. https://doi.org/10.1097/FTD.0b013e3181fcf94d
McAlpine, Donald E. ; Biernacka, Joanna M ; Mrazek, David A. ; O&apos;Kane, Dennis J. ; Stevens, Susanna R. ; Langman, Loralie J. ; Courson, Vicki L. ; Bhagia, Jyoti ; Moyer, Thomas P. / Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine. In: Therapeutic Drug Monitoring. 2011 ; Vol. 33, No. 1. pp. 14-20.
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