Evidence mapPaperPMID 42399684Full record

ArticlePediatric research2026

Interindividual variability in metformin pharmacokinetics in pediatric patients.

Anoud Sameer Ailabouni, Kelsee Halpin, Erin C Boone, Andrea Gaedigk, Takanobu Nadai, Kei Irie, Tomoyuki Mizuno, J Steven Leeder, Bhagwat Prasad

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Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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9 authors.

Anoud Sameer Ailabouni *Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, USA.
Kelsee Halpin *Division of Endocrinology and Diabetes, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO, USA.
Erin C BooneDepartment of Pediatrics, University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA.
Andrea GaedigkChildren's Mercy Research Institute, Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Kansas City, MO, USA.
Takanobu NadaiDivision of Translation and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Kei IrieDivision of Translation and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Tomoyuki MizunoDivision of Translation and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
J Steven LeederChildren's Mercy Research Institute, Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Kansas City, MO, USA.
Bhagwat PrasadDepartment of Pharmaceutical Sciences, Washington State University, Spokane, WA, USA. bhagwat.prasad@cchmc.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetformin is the first-line treatment for type 2 diabetes mellitus in pediatric patients and it's prescriptions in children have increased for off-label indications. However, interindividual variability of metformin pharmacokinetics in children is not well studied. Metformin is a cation that requires multiple transporters for its absorption, distribution and elimination, including organic cation transporters (OCTs) and multidrug and toxin extrusion (MATE) transporters.

methodsWe conducted a 12 h clinical pharmacokinetic study in 36 pediatric patients (age, 7-21 years) treated with metformin and analyzed the data using non-compartmental and population pharmacokinetic models to describe metformin pharmacokinetics and associated covariates. The association of OCT and MATE genetic variants on metformin absorption and elimination was investigated.

resultsThe dose-normalized plasma exposure of metformin varied by 3.3-fold among children. Renal clearance was higher in children compared to the reported data in healthy adults or adults with diabetes. Total body weight (TBW) and estimated glomerular filtration rate (eGFR) significantly affected metformin oral clearance. OCT2 c.390 G > T (p.Thr130 = , rs624249) was associated with metformin oral clearance and secretary clearance, whereas OCT3 c.-29G > A (rs555754) and c.360 C > T (p.Arg120 = , rs668871) were significantly associated with the absorption rate constant and oral clearance.

conclusionMetformin dosing in children can be optimized based on TBW, eGFR, and OCT2/3 genetic variants to improve its safety and efficacy. IMPACT: Metformin pharmacokinetics is highly variable, and limited data are available on the pediatric population. Total body weight and estimated glomerular filtration rate are associated with metformin oral clearance. OCT2/3 genetic variants can influence the elimination and absorption of metformin. Consideration of population factors associated with metformin pharmacokinetics in dose selection can improve its safety and efficacy.

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.