Key result
Simulated subcutaneous furosemide exposure in adolescents weighing >60-70 kg (AUC 13,000 µg⋅h/L) was similar to adults (12,400 µg⋅h/L), supporting an 80-mg fixed dose for adolescents weighing ≥42.5 kg.
Why the study?
Subcutaneous furosemide administered via an On-Body Infusor could be useful for children with heart failure and volume overload, but the appropriate dosing regimen is unknown.
What is the appropriate dosing regimen for subcutaneous furosemide in adolescents with heart failure and volume overload?
What is the appropriate dosing regimen for subcutaneous furosemide in adolescents with heart failure and volume overload?
Absolute Event Rate: 13000% vs 12400%
A population pharmacokinetic model supports an 80-mg dose of subcutaneous furosemide for adolescents aged 12-17 years with heart failure and volume overload weighing ≥ 42.5 kg.
May inform pediatric HF dosing; extends adult data but leaves open prospective validation.
BACKGROUND: Subcutaneous furosemide administered with the On-Body Infusor could be useful in children with heart failure (HF) and congestion due to volume overload, but the appropriate dosing regimen is unknown. OBJECTIVE: This study aimed to develop a population pharmacokinetic (popPK) model to determine the subcutaneous furosemide dosing regimen in children with HF who are appropriate for On-Body Infusor use. METHODS: Samples collected from 15 adults with HF who received subcutaneous or intravenous furosemide in a randomized phase II/III study (NCT02329834) were used to develop the popPK model with covariates identified by forward inclusion and backward elimination; validation was by bootstrapping. The model was allometrically scaled from a 70-kg adult body weight to simulate furosemide pharmacokinetics in virtual adolescents aged 12-17 years by weight category (42.5-50.0, > 50-60, and > 60-70 kg) for subcutaneous furosemide 80 mg (30 mg over 1 h then 12.5 mg/h for 4 h). RESULTS: Furosemide pharmacokinetics were best characterized using a two-compartment model with first-order absorption and elimination. After scaling to adolescents in subcutaneous dosing simulations, estimated furosemide clearance was 1.55 mL/min/kg. Estimated exposure (mean area under the plasma concentration-time curve at 24 h) was 16,800 µg⋅h/L in adolescents weighing 42.5-50.0 kg, 14,700 µg⋅h/L in adolescents weighing > 50-60 kg, and 13,000 µg⋅h/L in adolescents weighing > 60-70 kg versus 12,400 µg⋅h/L in adults. CONCLUSIONS: Simulated furosemide exposure was consistent with published values, supporting an 80-mg dose of subcutaneous furosemide (30 mg over the first hour, then 12.5 mg/h for 4 h) for adolescents aged 12-17 years with body weight ≥ 42.5 kg.
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Hornik et al. (2025) studied Heart Failure and Volume Overload (n=15). Subcutaneous furosemide vs. Intravenous furosemide (adults) / Typical 70-kg adult (simulations) was evaluated on Estimated exposure (area under the plasma concentration-time curve at 24 h, AUC 0-24). Simulated subcutaneous furosemide exposure in adolescents weighing >60-70 kg (AUC 13,000 µg⋅h/L) was similar to adults (12,400 µg⋅h/L), supporting an 80-mg fixed dose for adolescents weighing ≥42.5 kg.
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