Journal article
Delineating gene-environment effects using virtual twins of patients treated with clozapine
Sam Mostafa, Thomas MM Polasek, Chad Bousman, Amin Rostami-Hodjegan, Leslie JJ Sheffield, Ian Everall, Christos Pantelis, Carl MJ Kirkpatrick
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY | WILEY | Published : 2023
DOI: 10.1002/psp4.12886
Abstract
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 ge..
View full abstractGrants
Awarded by National Health and Medical Research Council of Australia
Awarded by National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship
Awarded by NHMRC L3 Investigator Grant
Funding Acknowledgements
The authors wish to acknowledge the Cooperative Research Centre (CRC) Scientific Advisory Committee, in addition to the contributions of study participants, clinicians at recruitment services, staff at the Murdoch Children's Research Institute, staff at the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging, and research staff at the Melbourne Neuropsychiatry Centre, including coordinators Phassouliotis, C., Merritt, A., and research assistants, Burnside, A., Cross, H., Gale, S., and Tahtalian, S. Participants for this study were sourced, in part, through the Australian Schizophrenia Research Bank (ASRB), which is supported by the National Health and Medical Research Council of Australia (Enabling Grant N. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. The authors acknowledge the financial support of The CRC Programme, an Australian Government Initiative. C.P. was supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1105825), an NHMRC L3 Investigator Grant (1196508). Certara UK Limited (Simcyp Division) granted access to the Simcyp Simulators through a sponsored academic license.