Delineating gene-environment effects using virtual twins of patients treated with clozapine.

Humans Clozapine / therapeutic use Antipsychotic Agents / therapeutic use Schizophrenia / drug therapy Genotype

Journal

CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306
Titre abrégé: CPT Pharmacometrics Syst Pharmacol
Pays: United States
ID NLM: 101580011

Informations de publication

Date de publication:
02 2023
Historique:
revised: 11 10 2022
received: 04 07 2022
accepted: 13 10 2022
pubmed: 26 11 2022
medline: 18 2 2023
entrez: 25 11 2022
Statut: ppublish

Résumé

Studies that focus on individual covariates, while ignoring their interactions, may not be adequate for model-informed precision dosing (MIPD) in any given patient. Genetic variations that influence protein synthesis should be studied in conjunction with environmental covariates, such as cigarette smoking. The aim of this study was to build virtual twins (VTs) of real patients receiving clozapine with interacting covariates related to genetics and environment and to delineate the impact of interacting covariates on predicted clozapine plasma concentrations. Clozapine-treated patients with schizophrenia (N = 42) with observed clozapine plasma concentrations, demographic, environmental, and genotype data were used to construct VTs in Simcyp. The effect of increased covariate virtualization was assessed by performing simulations under three conditions: "low" (demographic), "medium" (demographic and environmental interaction), and "high" (demographic and environmental/genotype interaction) covariate virtualization. Increasing covariate virtualization with interaction improved the coefficient of variation (R

Identifiants

DOI: 10.1002/psp4.12886 PMID: 36424701 PMC: PMC9931435
pubmed: 36424701
doi: 10.1002/psp4.12886
pmc: PMC9931435
doi:

Substances chimiques

Clozapine J60AR2IKIC
Antipsychotic Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

168-179

Informations de copyright

© 2022 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

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Auteurs

Sam Mostafa (S)

Centre for Medicine Use and Safety, Monash University, Victoria, Parkville, Australia.
MyDNA Life, Australia Limited, Victoria, South Yarra, Australia.

Thomas M Polasek (TM)

Centre for Medicine Use and Safety, Monash University, Victoria, Parkville, Australia.
Certara, New Jersey, Princeton, USA.
Department of Clinical Pharmacology, Royal Adelaide Hospital, South Australia, Adelaide, Australia.

Chad Bousman (C)

Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Victoria, Melbourne, Australia.
The Cooperative Research Centre (CRC) for Mental Health, Victoria, Melbourne, Australia.
Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Alberta, Calgary, Canada.
Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Alberta, Calgary, Canada.
Departments of Medical Genetics, Psychiatry, and Physiology and Pharmacology, University of Calgary, Alberta, Calgary, Canada.

Amin Rostami-Hodjegan (A)

Centre for Applied Pharmacokinetic Research (CAPKR), School of Health Sciences, University of Manchester, Manchester, UK.
Simcyp Division, Certara UK Limited, Sheffield, UK.
ORCID: 0000-0003-3917-844X

Leslie J Sheffield (LJ)

MyDNA Life, Australia Limited, Victoria, South Yarra, Australia.

Ian Everall (I)

Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Victoria, Melbourne, Australia.
The Cooperative Research Centre (CRC) for Mental Health, Victoria, Melbourne, Australia.
Western Australian Health Translation Network, Nedlands, Western Australia, Australia.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Melbourne, Australia.

Christos Pantelis (C)

Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Victoria, Melbourne, Australia.
The Cooperative Research Centre (CRC) for Mental Health, Victoria, Melbourne, Australia.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Melbourne, Australia.

Carl M J Kirkpatrick (CMJ)

Centre for Medicine Use and Safety, Monash University, Victoria, Parkville, Australia.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Delineating gene-environment effects using...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérocycliques 3 noyaux › Dibenzazépines › Clozapine › Delineating gene-environment effects using...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Psychoanaleptiques › Tranquillisants › Neuroleptiques › Delineating gene-environment effects using...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Schizophrénie › Delineating gene-environment effects using...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Delineating gene-environment effects using...