The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol

Clinical Pharmacology and Therapeutics
M JerlingF Sjöqvist

Abstract

Most antidepressant and neuroleptic agents are metabolized by the polymorphic cytochrome P450 enzyme CYP2D6. This study evaluates the importance of the CYP2D6 genotype for the disposition of the neuroleptic agents perphenazine and zuclopenthixol. Patients treated with neuroleptic agents (n = 36) were studied prospectively with regard to CYP2D6 genotype and neuroleptic plasma concentration during oral treatment. Because no patient provided enough samples for individual kinetic modeling, a bayesian approach was used for determination of the clearance. Population kinetic parameters for this procedure were collected from retrospective therapeutic drug monitoring data (n = 113) by use of a nonparametric approach. The CYP2D6 genotype significantly predicted the oral clearance of perphenazine and zuclopenthixol (p < 0.01 by multiple regression). The difference in clearance between homozygous extensive metabolizers and poor metabolizers was threefold for perphenazine and twofold for zuclopenthixol. The results show that the genotype for CYP2D6 is closely related to the oral clearances of perphenazine and zuclopenthixol. If this finding can be confirmed in a larger population, genotyping may become an important tool for the dosing of th...Continue Reading

References

Oct 1, 1976·British Journal of Clinical Pharmacology·C Eggert HansenE F Hvidberg
Jan 1, 1992·Clinical Pharmacology and Therapeutics·M L DahlF Sjöqvist
Apr 1, 1992·Therapeutic Drug Monitoring·A LlerenaL Bertilsson
Jun 1, 1992·Clinical Pharmacokinetics·A H Thomson, B Whiting
Jan 1, 1991·European Journal of Clinical Pharmacology·E SpinaJ Benitez
Jul 1, 1989·Clinical Pharmacology and Therapeutics·M L Dahl-PuustinenL Bertilsson
Jul 15, 1985·Biochemical Pharmacology·C von BahrF Sjöqvist
Jan 1, 1994·European Journal of Clinical Pharmacology·K BrøsenK Skjødt
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·I JohanssonM Ingelman-Sundberg
Apr 1, 1993·Pharmacogenetics·M L Dahl, L Bertilsson

❮ Previous
Next ❯

Citations

Feb 20, 2002·British Journal of Clinical Pharmacology·Leif BertilssonAyman Al-Shurbaji
May 23, 2000·Drug Metabolism and Drug Interactions·K J AitchisonT Sharma
Apr 26, 2002·Pharmacogenomics·Maria Gabriella Scordo, Edoardo Spina
Jul 23, 1999·Pharmacotherapy·C H Rojas-Fernandez, C MacKnight
Dec 28, 1999·Pharmacotherapy·B A HamelinM L Crismon
Feb 24, 2010·Australasian Psychiatry : Bulletin of Royal Australian and New Zealand College of Psychiatrists·Sean HoodSimon Davies
Mar 16, 2011·Expert Opinion on Drug Metabolism & Toxicology·Silvio CacciaMaurizio Bonati
Aug 23, 2006·Expert Opinion on Drug Metabolism & Toxicology·Wladyslawa Anna Daniel
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Apr 12, 2000·British Journal of Clinical Pharmacology·P B Mitchell
Oct 13, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Nov 12, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Oct 16, 2010·Acta Psychiatrica Scandinavica·S J C DaviesO Spigset
Jan 1, 1998·International Journal of Psychiatry in Clinical Practice·D ZullinoP Baumann
Jan 1, 1997·The British Journal of Psychiatry : the Journal of Mental Science·M ArmstrongJ R Idle
Jul 9, 2013·European Journal of Clinical Pharmacology·Jochem G GregoorEibert R Heerdink
Sep 10, 2014·Journal of Neural Transmission·Edoardo Spina, Jose de Leon
Oct 3, 1999·Journal of Clinical Psychopharmacology·V OzdemirC A Naranjo
Oct 21, 1998·Therapeutic Drug Monitoring·Y Caraco
Feb 25, 2000·Therapeutic Drug Monitoring·K Otani, T Aoshima
Sep 14, 2006·Pharmacological Reviews·Sharon J Gardiner, Evan J Begg
Nov 15, 2012·Therapeutic Drug Monitoring·Lisbeth PatteetHugo Neels
Apr 26, 2003·Journal of Clinical Pharmacy and Therapeutics·E Tanaka
Aug 26, 2011·Clinical Pharmacology and Therapeutics·M TodM C Gagnieu
Jan 3, 2001·British Journal of Clinical Pharmacology·O V Olesen, K Linnet
Oct 6, 1999·British Journal of Clinical Pharmacology·K J AitchisonR W Kerwin
Oct 30, 2020·British Journal of Clinical Pharmacology·Ragnhild Birkeland WaadeGudrun Høiseth
Dec 29, 2020·Frontiers in Genetics·Beatriz Carvalho HenriquesKatherine J Aitchison

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