Thorough QT/QTc in a Dish: An In Vitro Human Model That Accurately Predicts Clinical Concentration-QTc Relationships

• Published in: Clinical pharmacology and therapeutics Vol. 105; no. 5; p. 1175
• Main Authors: Blanchette, Alexander D, Grimm, Fabian A, Dalaijamts, Chimeddulam, Hsieh, Nan-Hung, Ferguson, Kyle, Luo, Yu-Syuan, Rusyn, Ivan, Chiu, Weihsueh A
• Format: Journal Article
• Language: English
• Published: United States 01.05.2019
• Subjects: Cardiotoxins - analysis; Cardiotoxins - pharmacokinetics; Drug Evaluation, Preclinical - methods; Drug-Related Side Effects and Adverse Reactions - diagnosis; Humans; In Vitro Techniques - methods; Induced Pluripotent Stem Cells; Long QT Syndrome - chemically induced; Long QT Syndrome - diagnosis; Models, Cardiovascular; Myocytes, Cardiac - drug effects; Predictive Value of Tests

"Thorough QT/corrected QT (QTc)" (TQT) studies are cornerstones of clinical cardiovascular safety assessment. However, TQT studies are resource intensive, and preclinical models predictive of the threshold of regulatory concern are lacking. We hypothesized that an in vitro model using indu...