title: In vitro-in vivo extrapolation of drug-induced proarrhythmia predictions at the population level.
abstract: Drug cardiotoxicity is a serious issue for patients, regulators, pharmaceutical companies and health service payers because they are all affected by its consequences. Despite the wide range of data they generate, existing approaches for cardiac safety testing might not be adequate and sufficiently cost-effective, probably as a result of the complexity of the problem. For this reason, translational tools (based on biophysically detailed, mathematical models) allowing for in vitro-in vivo extrapolation are gaining increasing interest. This current review describes approaches that can be used for cardiac safety assessment at the population level, by accounting for various sources of variability including kinetics of the compound of interest.
authors.affiliation: Unit of Pharmacoepidemiology and Pharmacoeconomics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland; Simcyp Limited, Blades Enterprise Centre, John Street, Sheffield, UK. Electronic address: spolak@cm-uj.krakow.pl.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Polak
authors.affiliation: Unit of Pharmacoepidemiology and Pharmacoeconomics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wiśniowska
authors.affiliation: Department of Statistics, Faculty of Management, Cracow University of Economics, Rakowicka 27 Street, 31-510 Kraków, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Fijorek
authors.affiliation: Unit of Pharmacoepidemiology and Pharmacoeconomics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Glinka
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Mendyk
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D066126:Cardiotoxicity / Q000209:etiology*; D003362:Cost-Benefit Analysis; D006801:Humans; D008962:Models, Theoretical; D018675:Toxicity Tests / Q000191:economics / Q000379:methods; D057170:Translational Research, Biomedical / Q000379:methods