Active Ingredient: PONATINIB
Ponatinib is a BCR-ABL tyrosine kinase inhibitor used in refractory hematological malignancies that demonstrates a low risk of QTc prolongation. In a phase 1 clinical study across three dose levels (30, 45, and 60 mg), mean QTcF changes from baseline were non-clinically significant and negative (-10.9 ms, -3.6 ms, and -5.0 ms, respectively). Pharmacokinetic-pharmacodynamic modeling confirmed a negative slope (-0.0171), indicating no exposure-response relationship. In vitro, hERG inhibition occurs only at supratherapeutic concentrations (> 1 uM vs clinical Cmax of 0.145 uM). A patient with QTcF > 500 ms was receiving concomitant QT-prolonging therapy (propoxyphene).
https://doi.org/10.1007/s00280-013-2160-7