Empagliflozin in paediatric heart failure: model-based optimisation of a pharmacokinetic bridging study

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Source: Frontiers Medicine

Original: https://www.frontiersin.org/articles/10.3389/fmed.2025.1522131...

Published: 2026-02-23T00:00:00Z

The study used mixed effects modeling to extrapolate the pharmacokinetics of empagliflozin from adults to children ≥15 kg with heart failure. They identified a two-compartment model with an allometric change in clearance parameters and weight distribution. At 10 mg in a 15 kg child, they achieved a median AUC ratio of 1.03 (interquartile range 0.82–1.30) versus a 50 kg adult at 25 mg (median 7,385,163 nmolh/l). They proposed an optimal sampling scheme for a study with 12 patients in 4 groups. This design allows drug exposure to be characterized and safety and efficacy data to be collected. The protocol envisages the extrapolation of the cardioprotective mechanisms of SGLT-2 inhibitors from adults to children. The results support the use of 10 mg tablets in children weighing ≥ 15 kg.