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Abstract Context of research Ferric maltol is an effective oral iron therapy in adults, but its pharmacokinetics (PK) in children are not well studied. Before this study, infant glucuronidation and urinary excretion of maltol were unknown, despite evidence in adults and older children. The study followed the Declaration of Helsinki and Good Clinical Practice with parental consent, patient assent as required, and addressed the information gap (NCT05126901). Methods Maltol glucuronide levels and baseline-corrected serum iron were evaluated in two groups. Twenty children (2-17 years) participated in the PK study over two assessment days (Day 1 & Day 7-10). On Day 1, after a baseline blood sample, they received a single supervised ferric maltol dose (iron equivalent at 15mg or 30mg doses), followed by PK sampling. Then, twice-daily (BID) dosing of the same dosage continued until Day 7-10, when the morning dose was withheld, and the PK procedure was repeated. Three infants (aged 1 month to <2 years) completed a one-day PK assessment with a single 0.6 mg/kg iron equivalent dose of ferric maltol. To reduce invasiveness in infants, PK was only based on urine sampling. Urine samples collected over 12 hours were analyzed for drug metabolism. If no accumulation of maltol or its metabolites was found, 0.6mg/kg BID dosing continued for 7–10 days. On Day 7–10, after baseline sampling, the same dose was given, followed by PK blood sampling (1–12 hours) and urine collection (0.5–12 hours). Findings PK results on Day 1 for plasma maltol glucuronide: In children aged 2–9 years receiving 15 mg, the maximum plasma concentration (Cmax) was 4350 ng/mL, reached at time to maximum plasma concentration (Tmax) of 1.00 hour with an area under the curve (AUC0–t) of 4670 h×ng/mL. Whereas those aged 10–17 years receiving the same 15 mg dose, the Cmax was 6810 ng/mL, reached at Tmax of 2.13 hours, with an AUC0–t of 12000 h×ng/mL. For the 30 mg dose in the 10–17 years group, the Cmax was 6420 ng/mL, reached at Tmax of 0.52 hours, with an AUC0–t of 14600 h×ng/mL. PK results on Day 7-10 for plasma maltol glucuronide: In the 2–9 years group receiving 15 mg, the Cmax was 4250 ng/mL, reached at Tmax of 0.98 hours, with an AUC0–t of 5900 h×ng/mL. Whereas those aged 10–17 years receiving the same 15 mg dose, the Cmax was 5940 ng/mL, reached at Tmax of 2.78 hours, with an AUC0–t of 8070 h×ng/mL. For the 30 mg dose in the 10–17 years group, the Cmaxwas 8160 ng/mL, reached at Tmax of 3.63 hours, with an AUC0–t of 16700 h×ng/mL. These findings showed that maltol was rapidly metabolized to maltol glucuronide, with Cmaxfor the metabolite recorded between 0.5 and 3.6 hours. By Day 7-10, pre-dose maltol glucuronide levels were undetectable in plasma, demonstrating nil accumulation. PK results for plasma maltol glucuronide in infants: Infants receiving ferric maltol 0.6 mg/kg showed mean urine maltol glucuronide concentrations of 153, 28.6, and 3.11 µg/mL, corresponding to maltol concentrations of 0.527, 0.103 µg/mL and not calculable at the last interval, at 0.5–3, 3–6, and 7–12 hours post-dose, respectively. These data confirm metabolism to the glucuronide, urinary excretion, in all patients, and no evidence of accumulation in infants. PK results on Day 1 for baseline-corrected serum iron: In the 2–9 years group receiving 15 mg, the Cmax was 87.0 µg/dL, reached at Tmax of 2.37 hours, with an AUC0–t of 64.4 h×µg/dL. For 10–17-year-olds receiving 15 mg dose, the Cmax was 40.0 µg/dL, reached at Tmax of 2.13 hours, with an AUC0–t of 60.1 h×µg/dL. In the 10–17 years group receiving a 30 mg dose, the Cmax was 119 µg/dL, reached at Tmax of 2.00 hours, with an AUC0–t of 374 h×µg/dL. PK results on Day 7-10 for baseline-corrected serum iron: In the 2–9 years group receiving 15 mg, the Cmax was 96.5 µg/dL, reached at Tmax of 2.10 hours, with an AUC0–t of 100 h×µg/dL. In the 10–17 years group receiving 15 mg dose, the Cmax was 21.0 µg/dL, reached at Tmax of 2.78 hours with an AUC0–t of 1.93 h×µg/dL. For the 10–17 years group receiving 30 mg, the Cmax was 364 µg/dL, reached at Tmax of 6.63 hours, with an AUC0–t of 1180 h×µg/dL. Conclusions The PK profile in children and adolescents demonstrated ferric maltol's suitability for iron replacement in all age groups; iron was well-absorbed and maltol was rapidly metabolized and excreted in the urine, with no accumulation of maltol or its metabolite.