Impact of multiple inhibitors or substrates of cytochrome P450 2D6 on plasma risperidone levels in patients on polypharmacy

Therapeutic Drug Monitoring
Buster MannheimerErik Eliasson

Abstract

Studies that focus on multidrug interactions in natural settings are sparse. In this investigation, data from therapeutic drug monitoring (TDM) were used to study the impact of multiple cytochrome P450 enzyme (CYP) 2D6 substrates and inhibitors on plasma risperidone levels. CYP2D6 catalyzes the conversion of risperidone to the active metabolite 9-OH-risperidone. The question whether CYP2D6 activity is important for the level of the "active moiety" (ie, the sum of risperidone and 9-OH-risperidone) is controversial. Concentration-to-dose (C:D) ratios of risperidone and 9-OH-risperidone in 218 patients were associated with the number of concomitantly used substrates or inhibitors of CYP2D6. The C:D ratios of risperidone in patients with 0, 1, and >1 numbers of CYP2D6 inhibitors were 2.6, 8.5, and 17 nmol L mg, respectively. Differences between the groups were highly significant (P < 0.001). All patients with >1 CYP2D6 inhibitors were administered at least 1 potent CYP2D6 inhibitor, that is fluoxetine, paroxetine, thioridazine, and/or levomepromazine. The C:D ratios of the active moiety (risperidone + 9-OH-risperidone) in patients with 0, 1, and >1 numbers of concomitant CYP2D6 inhibitors were 17, 24, and 30 nmol L mg, respectively...Continue Reading

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Citations

Jun 2, 2010·The Pharmacogenomics Journal·B OnedaC B Eap
Jan 19, 2013·Pharmacogenomics·Adrián LlerenaHumberto Fariñas
Mar 20, 2014·European Journal of Clinical Pharmacology·Buster MannheimerErik Eliasson
Feb 25, 2015·International Journal of Molecular Sciences·Teri SmithMerlin G Butler
Sep 30, 2015·Therapeutic Drug Monitoring·Buster MannheimerEspen Molden
Feb 16, 2016·Expert Opinion on Drug Metabolism & Toxicology·Edoardo SpinaJose de Leon
Jul 2, 2015·Clinical Pharmacokinetics·Frederik VandenbergheChin B Eap
Mar 5, 2016·Applied & Translational Genomics·Tyren M DodgenMichael S Pepper
Jul 28, 2017·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·S S PetersS H Wrzesinski
Apr 9, 2019·Therapeutic Advances in Psychopharmacology·Emma TayRichard O Day
Jun 11, 2020·Journal of Neural Transmission·Gudrun HefnerAnsgar Klimke
Nov 28, 2020·Journal of Analytical Toxicology·Sarah M R Wille, Simon Elliott
Dec 29, 2020·Frontiers in Genetics·Beatriz Carvalho HenriquesKatherine J Aitchison

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