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However, interindividual variability of metformin pharmacokinetics in children is not well studied. Metformin is a cation that\u00a0requires multiple transporters\u00a0for its absorption, distribution and elimination, including organic cation transporters (OCTs) and multidrug and toxin extrusion (MATE) transporters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a 12\u2009h clinical pharmacokinetic study in 36 pediatric patients\u00a0(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\n                      <jats:italic>OCT<\/jats:italic>\n                      and\n                      <jats:italic>MATE<\/jats:italic>\n                      genetic variants on metformin absorption and elimination\u00a0was investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 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.\n                      <jats:italic>OCT2<\/jats:italic>\n                      c.390\u2009G\u2009&gt;\u2009T (p.Thr130\u2009=\u2009, rs624249) was associated with metformin oral clearance and secretary clearance, whereas\n                      <jats:italic>OCT3<\/jats:italic>\n                      c.-29G\u2009&gt;\u2009A (rs555754) and c.360\u2009C\u2009&gt;\u2009T (p.Arg120\u2009=\u2009, rs668871) were significantly associated with the absorption rate constant and oral clearance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Metformin dosing in children can be optimized based on TBW, eGFR, and\n                      <jats:italic>OCT2\/3<\/jats:italic>\n                      genetic variants to improve its safety and efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Metformin pharmacokinetics is highly variable, and limited data are available on the pediatric population.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Total body weight and estimated glomerular filtration rate are associated with metformin oral clearance.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>OCT2\/3<\/jats:italic>\n                            genetic variants can influence the elimination and absorption of metformin.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Consideration of population factors associated with metformin pharmacokinetics in dose selection can improve its safety and efficacy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-026-04938-0","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T16:33:13Z","timestamp":1783096393000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interindividual variability in metformin pharmacokinetics in pediatric patients"],"prefix":"10.1038","author":[{"given":"Anoud Sameer","family":"Ailabouni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsee","family":"Halpin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin C.","family":"Boone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gaedigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanobu","family":"Nadai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Irie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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