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In order to assess drug\u2010induced TdP risks, a model of cardiac ionic current suppression in human ventricular myocytes (ToR\u2010ORd model), combined with the maximum effective free therapeutic plasma concentration or the maximum effective free therapeutic myocyte concentration was often used, with the latter proved to be more relevant and more accurate. We aimed to develop a whole\u2010body physiologically\u2010based pharmacokinetic (PBPK) model, incorporated with a human cardiomyocyte pharmacodynamic (PD) model, to provide a comprehensive assessment of drug\u2010induced TdP risks in normal and specific scenarios. Quinidine served as an example to validate the PBPK\u2010PD model via predicting plasma quinidine concentrations and quinidine\u2010induced changes in QT interval (\u0394QTc). The predicted plasma quinidine concentrations and \u0394QTc values following oral administration or intravenous administration of quinidine were comparable to clinic observations. Visual predictive checks showed that most of the observed plasma concentrations and \u0394QTc values fell within the 5th and 95th percentiles of simulations. The validated PBPK\u2010PD model was further applied to assess the TdP risks using frequencies of early afterdepolarization and long\u2010QT syndrome occurrence in 4 scenarios, such as therapeutic dose, supra\u2010therapeutic dose, alkalosis, and hyperkalemia in 200 human subjects. In conclusion, the developed PBPK\u2010PD model may be applied to predict the quinidine pharmacokinetics and quinidine\u2010induced TdP risks in healthy subjects, but also simulate quinidine\u2010induced TdP risks under disease conditions, such as hypokalemia and alkalosis.<\/jats:p>","DOI":"10.1002\/cpt.3156","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T15:05:41Z","timestamp":1703084741000},"page":"616-626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of Quinidine\u2010Induced Torsades de Pointes Risks Using a Whole\u2010Body Physiologically Based Pharmacokinetic Model Linked to Cardiac Ionic Current Inhibition"],"prefix":"10.1002","volume":"115","author":[{"given":"Zexin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy China Pharmaceutical University  Nanjing 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