QT PRODACT: Comparison of Non-clinical Studies for Drug-Induced Delay in Ventricular Repolarization and Their Role in Safety Evaluation in Humans

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Population

In vitro assays using guinea-pig papillary muscle and in vivo assays using conscious dogs, conscious…

Comparison

Torsadogenic compounds vs Comparison between in vitro and in vivo assays…

Design

Preclinical

Authors

Discussion

Supports preclinical QT safety margin estimation across species; leaves open human torsades translation pending clinical validation.

Population

In vitro assays using guinea-pig papillary muscle and in vivo assays using conscious dogs, conscious monkeys, and anesthetized dogs

Intervention

Torsadogenic compounds (drugs that prolong QTc interval)

Comparator

Comparison between in vitro and in vivo assays, and among different in vivo models

Outcome

Drug concentrations that prolong repolarization parameters by 10% (EC10 values for APD90, APD30-90, and QTc intervals)surrogate

In vivo QT assays in dogs and monkeys are highly consistent and useful for estimating the safety margin of drugs that prolong the QTc interval.

Omata et al. (2005) studied this question.

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