CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 10 2023
28 10 2023
Historique:
received:
10
03
2023
accepted:
23
10
2023
medline:
30
10
2023
pubmed:
29
10
2023
entrez:
29
10
2023
Statut:
epublish
Résumé
Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of - 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying - 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients' olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients' olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage.
Identifiants
pubmed: 37898643
doi: 10.1038/s41598-023-45752-6
pii: 10.1038/s41598-023-45752-6
pmc: PMC10613299
doi:
Substances chimiques
Olanzapine
N7U69T4SZR
Cytochrome P-450 CYP1A2
EC 1.14.14.1
Cytochrome P-450 CYP2D6
EC 1.14.14.1
Antipsychotic Agents
0
RNA, Messenger
0
CYP1A2 protein, human
EC 1.14.14.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18507Informations de copyright
© 2023. The Author(s).
Références
Br J Psychiatry Suppl. 1999;(37):36-40
pubmed: 10211140
Clin Pharmacol Ther. 2012 Oct;92(4):511-9
pubmed: 22948892
Front Pharmacol. 2021 Jul 14;12:711940
pubmed: 34335273
Br J Clin Pharmacol. 2015 Feb;79(2):222-40
pubmed: 24913012
Pharmacogenomics. 2013 Aug;14(11):1319-36
pubmed: 23930678
Patient Prefer Adherence. 2011;5:547-54
pubmed: 22114469
Lancet. 2016 Jul 2;388(10039):86-97
pubmed: 26777917
Drug Metab Dispos. 1997 Jan;25(1):81-93
pubmed: 9010634
J Neural Transm (Vienna). 2015 Jan;122(1):35-42
pubmed: 25047911
Am J Hum Genet. 2005 Mar;76(3):449-62
pubmed: 15700229
Br J Clin Pharmacol. 2002 Nov;54(5):540-3
pubmed: 12445035
Clin Transl Sci. 2019 Jan;12(1):39-46
pubmed: 30387917
Genet Med. 2017 Jan;19(1):69-76
pubmed: 27388693
Xenobiotica. 2021 Mar;51(3):279-286
pubmed: 33350342
Pharmacogenomics. 2002 Mar;3(2):229-43
pubmed: 11972444
Acta Psychiatr Scand. 2019 Jan;139(1):15-25
pubmed: 30112761
Clin Pharmacol Ther. 2021 Sep;110(3):563-572
pubmed: 34216021
Pharmacogenomics. 2008 May;9(5):625-37
pubmed: 18466106
Eur J Clin Pharmacol. 2010 May;66(5):465-74
pubmed: 20143052
J Biochem. 1999 Apr;125(4):803-8
pubmed: 10101295
Pharmacol Ther. 2013 Apr;138(1):103-41
pubmed: 23333322
Ther Drug Monit. 2003 Feb;25(1):46-53
pubmed: 12548144
J Gerontol A Biol Sci Med Sci. 2012 Feb;67(2):175-80
pubmed: 21835808
Shanghai Arch Psychiatry. 2018 Jun 25;30(3):178-187
pubmed: 30858669
Bioorg Med Chem Lett. 2013 Apr 1;23(7):1953-6
pubmed: 23466228
Br J Clin Pharmacol. 1999 Apr;47(4):445-9
pubmed: 10233211
Am J Hum Genet. 2001 Apr;68(4):978-89
pubmed: 11254454
J Pharmacol Exp Ther. 2012 Apr;341(1):294-305
pubmed: 22262920
J Mol Diagn. 2021 Sep;23(9):1047-1064
pubmed: 34118403
Pharmacopsychiatry. 2011 Sep;44(6):195-235
pubmed: 21969060
Br J Psychiatry. 2011 Jan;198(1):6-7
pubmed: 21200069
Pharmacogenomics J. 2005;5(1):6-13
pubmed: 15492763
Ther Drug Monit. 2008 Feb;30(1):35-40
pubmed: 18223460
Handb Exp Pharmacol. 2012;(212):241-65
pubmed: 23129335
Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr;26(3):529-37
pubmed: 11999904
Expert Opin Drug Metab Toxicol. 2013 Sep;9(9):1115-37
pubmed: 23641727
Drugs. 2001;61(1):111-61
pubmed: 11217867
Nucleic Acids Res. 2022 Jan 7;50(D1):D1216-D1220
pubmed: 34718739
Pharmacogenomics J. 2020 Apr;20(2):192-201
pubmed: 31616047
J Clin Psychopharmacol. 2007 Aug;27(4):329-37
pubmed: 17632215
Pharmacogenomics J. 2013 Dec;13(6):544-50
pubmed: 23147717
Pharmacol Rep. 2020 Dec;72(6):1695-1705
pubmed: 32638224
Front Pharmacol. 2021 Aug 26;12:730637
pubmed: 34512355
Biomed Res Int. 2014;2014:656370
pubmed: 24995318
Int Rev Neurobiol. 2008;83:1-10
pubmed: 18929073
Drug Metab Dispos. 2015 Nov;43(11):1806-14
pubmed: 26329789
Pharmacogenomics J. 2009 Feb;9(1):34-41
pubmed: 18591960
J Clin Psychopharmacol. 2011 Feb;31(1):4-9
pubmed: 21192135
Pharmacogenomics J. 2018 Dec;18(6):760-768
pubmed: 29282363
Ther Drug Monit. 2015 Apr;37(2):152-60
pubmed: 25090458
Bioinformatics. 2005 Jan 15;21(2):263-5
pubmed: 15297300
Hum Mutat. 2001 Apr;17(4):355-6
pubmed: 11295848
Biomed Pharmacother. 2021 Jan;133:111087
pubmed: 33378980
Curr Med Res Opin. 2010 Oct;26(10):2403-10
pubmed: 20812791
Nat Rev Dis Primers. 2018 Mar 08;4:18008
pubmed: 29516993
Pharmacogenomics. 2020 Apr;21(6):369-373
pubmed: 32308139
Eur J Clin Pharmacol. 2005 Dec;61(12):887-92
pubmed: 16307269
J Clin Psychopharmacol. 2005 Dec;25(6):570-4
pubmed: 16282840
Int J Clin Pract. 2008 May;62(5):837-40
pubmed: 18412940
Schizophrenia (Heidelb). 2022 Feb 28;8(1):9
pubmed: 35228573
Clin Pharmacol Ther. 2012 Aug;92(2):221-7
pubmed: 22713701
J Clin Pharmacol. 2008 Feb;48(2):157-65
pubmed: 18199892
Clin Pharmacol Ther. 2004 Dec;76(6):598-606
pubmed: 15592331
Eur J Clin Pharmacol. 2007 Jun;63(6):537-46
pubmed: 17370067
Curr Med Chem. 2009;16(31):4066-218
pubmed: 19754423
Arch Biochem Biophys. 2001 Sep 15;393(2):308-15
pubmed: 11556818
Pharmacogenomics J. 2010 Feb;10(1):20-9
pubmed: 19636338
Expert Opin Drug Metab Toxicol. 2018 Mar;14(3):275-285
pubmed: 29431542
Clin Pharmacol Ther. 2004 Aug;76(2):128-38
pubmed: 15289790
Clin Pharmacol Ther. 2019 Jul;106(1):94-102
pubmed: 30801677
J Clin Psychopharmacol. 2003 Apr;23(2):119-27
pubmed: 12640212
Int J Obes Relat Metab Disord. 1995 Apr;19(4):234-9
pubmed: 7627246
Clin Pharmacol Ther. 2011 Jul;90(1):117-25
pubmed: 21593735
Eur J Clin Pharmacol. 2010 Jul;66(7):697-703
pubmed: 20390257
Clin Pharmacol Ther. 2020 Jan;107(1):154-170
pubmed: 31544239
Front Pharmacol. 2010 Nov 02;1:129
pubmed: 21918647
J Pharmacol Exp Ther. 1996 Feb;276(2):658-66
pubmed: 8632334
AAPS J. 2009 Sep;11(3):481-94
pubmed: 19590965
Basic Clin Pharmacol Toxicol. 2020 Mar;126(3):183-192
pubmed: 31908124
Drug Metab Rev. 2010 May;42(2):268-354
pubmed: 19961320
Pharmaceutics. 2022 Feb 27;14(3):
pubmed: 35335907