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Electrophysiological in vitro and in vivo studies indicate an overall moderate risk of domperidone to prolong the QT interval in humansIn in vitro experiments on isolated cells transfected with hERG and on isolated guinea pig myocytesexposure ratios ranged between 2647-foldbased on IC50 values inhibiting currents through IKr ion channels in comparison to the free plasma concentrations in humans after administration of the maximum daily dose of 10 mg administered 3 times a daySafety margins for prolongation of action potential duration in in vitro experiments on isolated cardiac tissues exceeded the free plasma concentrations in humans at maximum daily dose10 mg administered 3 times a dayby 45-foldSafety margins in in vitro pro-arrhythmic modelsisolated Langendorff perfused heartexceeded the free plasma concentrations in humans at maximum daily dose10 mg administered 3 times a dayby 9up to 45-foldIn in vivo models the no effect levels for QTc prolongation in dogs and induction of arrhythmias in a rabbit model sensitized for torsade de pointes exceeded the free plasma concentrations in humans at maximum daily dose10 mg administered 3 times a dayby more than 22-fold and 435-foldrespectivelyIn the anesthetized guinea pig model following slow intravenous infusionsthere were no effects on QTc at total plasma concentrations of 45.4 ng/mLwhich are 3-fold higher than the total plasma levels in humans at maximum daily dose10 mg administered 3 times a dayThe relevance of the latter study for humans following exposure to orally administered domperidone is uncertain.

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