ArticleCPT: pharmacometrics & systems pharmacology2023
Delineating gene-environment effects using virtual twins of patients treated with clozapine.
Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Seeing what is behind the smokescreen: A systematic review of methodological aspects of smoking interaction studies over the last three decades and implications for future clinical trials.Clinical and translational science · 2023Pooled it
- Application of Virtual Twin PBPK Models in Individuals with Obesity via CYP3A4 Phenotyping Using Endogenous Biomarker Data.Clinical pharmacology and therapeutics · 2026Article
- A Review of Virtual Twins in Physiologically-Based Pharmacokinetic Modeling and Simulation.Clinical pharmacology and therapeutics · 2026Review
- From Therapeutic Drug to Xenobiotic in Cancer Repurposing: Clozapine Mechanisms, Metabolic Liabilities, and Human-Relevant Translational Approaches.Journal of xenobiotics · 2026Review
- Virtual Twin Approach Using Physiologically Based Pharmacokinetic Modeling to Support Precision Dosing of Valproic Acid in Geriatric Patients.Clinical pharmacology and therapeutics · 2026Article
- Model-Based Virtual Clinical Trial Reveals Renal Impairment and Body Size as Key Determinants of Pharmacokinetic Variability and Drug-Drug Interaction Risk in Propranolol Therapy.Pharmaceutics · 2026Article
- Physiologically-Based Pharmacokinetic Modeling to Investigate Piperaquine Exposure in Pregnant Women Using an Individualized Profile Approach.Clinical and translational science · 2026Article
- Physiologically Based Pharmacokinetic Virtual Twin Approach for Fludarabine Dosing in Pediatric Hematopoietic Stem Cell Transplantation.CPT: pharmacometrics & systems pharmacology · 2026Article
- From Population-Based PBPK to Individualized Virtual Twins: Clinical Validation and Applications in Medicine.Journal of clinical medicine · 2026Review
- Amikacin Dosing Adjustment in Critically Ill Oncologic Patients: A Study with Real-World Patients, PBPK Analysis, and Digital Twins.Pharmaceutics · 2025Article
- Virtual twins for model-informed precision dosing of clozapine in patients with treatment-resistant schizophrenia.CPT: pharmacometrics & systems pharmacology · 2024Article
- Delineating gene-environment effects using virtual twins of patients treated with clozapine.CPT: pharmacometrics & systems pharmacology · 2023Article
- Virtual twin for healthcare management.Frontiers in digital health · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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 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
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.