{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:17:35Z","timestamp":1784085455499,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Childhood obesity continues to rise in the United States and, with it, the off\u2010label use of metformin for weight loss. The influence of age and obesity on the drug's disposition and exposure has not previously been studied using a mechanistic framework. Here, an adult physiologically based pharmacokinetic (PBPK) model of metformin was scaled to pediatric populations without obesity, with overweight\/obesity, and with severe obesity; a published virtual population of children and adolescents with obesity was leveraged during model evaluation. When the pediatric model was simulated in groups aged 10 to 18 years, oral clearance following 1000\u00a0mg of metformin was higher (\u22481200\u00a0mL\/min) in those with obesity and severe obesity compared to the groups without and with overweight (\u22481000\u00a0mL\/min). In addition, simulated area under the concentration\u2010time curve in older children and adolescents with obesity and severe obesity was comparable to that in adults with a similar dose\u2010exposure relationship. Overall, simulations using the pediatric PBPK model support the use of adult doses of metformin in older children and adolescents with obesity. Moreover, the virtual population of children and adolescents with obesity offers a valuable tool to facilitate development of pediatric PBPK models for studying populations with obesity and, in turn, contribute information to inform drug labeling in this special population.<\/jats:p>","DOI":"10.1002\/jcph.2034","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T13:12:55Z","timestamp":1643980375000},"page":"960-969","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Physiologically Based Pharmacokinetic Modeling of Metformin in Children and Adolescents With Obesity"],"prefix":"10.1002","volume":"62","author":[{"given":"Jennifer Lynn","family":"Ford","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics UNC Eshelman School of Pharmacy The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline G.","family":"Gerhart","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics UNC Eshelman School of Pharmacy The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea N.","family":"Edginton","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo  Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack A.","family":"Yanovski","sequence":"additional","affiliation":[{"name":"Section on Growth and Obesity, Program in Developmental Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuen Yi","family":"Hon","sequence":"additional","affiliation":[{"name":"Clinical Pharmacokinetics Research Laboratory Clinical Center Pharmacy Department National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics UNC Eshelman School of Pharmacy The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.14590"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000060923.07573.F2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028014557859"},{"key":"e_1_2_10_5_1","volume-title":"Glucophage\u00ae (metformin hydrochloride) tablets [package insert]","year":"2017"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S95299"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/11534750-000000000-00000"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199630050-00003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1996.tb00017.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00896-w"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035092"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2018.1440287"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2165\/11593970-000000000-00000"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-018-0293-1"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.796"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01072-4"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2014.45"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.176"},{"key":"e_1_2_10_19_1","unstructured":"Bayer Technology Services. 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