Active Ingredient: PAZOPANIB
Pazopanib, a multikinase inhibitor targeting VEGFR, PDGFR, and c-Kit, was evaluated for electrocardiographic effects in a double-blind, placebo-controlled study in cancer patients (N = 96, 65 evaluable) with moxifloxacin positive control, therapeutic dosing (800 mg/day fasted), and supratherapeutic exposure (1600 mg with food, achieving 1.3- to 1.4-fold clinical exposure). On Day 9, the maximum mean placebo-adjusted, baseline-corrected QTcF difference was 4.4 ms (90% CI: -2.4 to 11.2 ms). Mixed-effects modeling indicated no significant concentration-dependent relationship between pazopanib or its metabolites and QTcF prolongation, although exposure correlated with anticipated increases in blood pressure and unexpected heart rate reductions. Overall, supratherapeutic pazopanib exposure produces a modest, concentration-independent QTcF prolongation with upper confidence bounds marginally crossing 10 ms.
https://doi.org/10.1007/s00280-012-2030-8, https://doi.org/10.1007/s40264-013-0047-5