{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:30:20Z","timestamp":1791927020643,"version":"4.3.4"},"reference-count":110,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Canary Islands Health Research Institute Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Despite the progressive increase in obesity and associated chronic diseases in children, there is limited evidence on the optimal dosage of most medications for obese children and adolescents. This review analyzes the influence of pathophysiological changes on pharmacokinetics and pharmacodynamics and evaluates the body size descriptors used in clinical practice. Patients with obesity present significant pathophysiological alterations, such as a substantial increase in fat\/lean mass ratio, increased blood flow and cardiac output, and changes in plasma protein binding, which may affect the volume of distribution of drugs and the adjustment of the loading dose. In these patients, the distribution volume of hydrophilic drugs appears to slightly increase, while it varies widely\u2014depending on the drug and other factors such as affinity for other tissues\u2014for lipophilic drugs. On the other hand, a reduction in tissue perfusion, alterations to liver enzyme activity, and an increase in liver and kidney mass and blood flow have been reported, indicating a possible modification in drug clearance and necessitating adjustments to maintenance regimens. Furthermore, while there are multiple size descriptors, it is difficult to establish a single dosing strategy for the obese population, given the lack of studies confirming the extent of changes in pharmacokinetic processes, which will also depend on the properties of each drug, such as liposolubility and elimination pathways. New strategies need to be developed to characterize pharmacokinetic and pharmacodynamic changes in the obese pediatric population in order to optimize dosing regimens and improve the safety and efficacy of treatments.<\/jats:p>","DOI":"10.3390\/ph19010016","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T07:01:33Z","timestamp":1766386893000},"page":"16","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics and Childhood Obesity: Pathophysiological Basis and Challenges in Choosing the Ideal Body Size Descriptor"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5074-8728","authenticated-orcid":false,"given":"Yolanda","family":"Hern\u00e1ndez-Gago","sequence":"first","affiliation":[{"name":"Department of Hospital Pharmacy, Insular Maternal and Child University Hospital Complex, 35016 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2985-3686","authenticated-orcid":false,"given":"Jos\u00e9 Germ\u00e1n","family":"S\u00e1nchez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Salamanca University Healthcare Complex, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4737-5638","authenticated-orcid":false,"given":"Pedro J. Alcal\u00e1","family":"Minagorre","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Alicante Institute for Health and Biomedical Research (ISABIAL), Dr. Balmis University General Hospital, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7208-5766","authenticated-orcid":false,"given":"Bel\u00e9n Rodr\u00edguez","family":"Rodr\u00edguez-Marrod\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Puerta de Hierro University Hospital, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4648-1721","authenticated-orcid":false,"given":"Laura Hern\u00e1ndez","family":"Hern\u00e1ndez Sabater","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwest Regional Hospital, 30400 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-2715","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9 Caba\u00f1as","family":"Poy","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Hospital Universitario Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Rodr\u00edguez","family":"Negr\u00edn","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Insular Maternal and Child University Hospital Complex, 35016 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1001\/jamapediatrics.2024.1576","article-title":"Global Prevalence of Overweight and Obesity in Children and Adolescents: A Systematic Review and Meta-Analysis","volume":"178","author":"Zhang","year":"2024","journal-title":"JAMA Pediatr."},{"key":"ref_2","unstructured":"UNICEF (2025, September 15). Feeding Profit. How Food Environments Are Failing Children. Child Nutrition Report 2025. Available online: https:\/\/www.unicef.org\/reports\/feeding-profit."},{"key":"ref_3","unstructured":"World Health Organization (2025, May 07). Obesity and Overweight. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_4","unstructured":"GBD 2021 Adult BMI Collaborators (2025). Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990-2021, with forecasts to 2050: A forecasting study for the Global Burden of Disease Study 2021. Lancet, 405, 785\u2013812."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/joim.13547","article-title":"Pediatric obesity-Long-term consequences and effect of weight loss","volume":"292","author":"Marcus","year":"2022","journal-title":"J. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3945\/an.115.008946","article-title":"Obesity in Childhood Cancer Survivors: Call for Early Weight Management","volume":"6","author":"Zhang","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13052-018-0525-6","article-title":"Diagnosis, treatment and prevention of pediatric obesity: Consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics","volume":"44","author":"Valerio","year":"2018","journal-title":"Ital. J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1177\/0009922814533406","article-title":"Pediatric obesity and safety in inpatient settings: A systematic literature review","volume":"53","author":"Halvorson","year":"2014","journal-title":"Clin. Pediatr."},{"key":"ref_9","first-page":"154","article-title":"Medication Errors in Overweight and Obese Pediatric Patients: A Narrative Review","volume":"48","author":"Procaccini","year":"2022","journal-title":"Jt. Comm. J. Qual. Patient Saf."},{"key":"ref_10","first-page":"S10","article-title":"Developmental Changes in Pharmacokinetics and Pharmacodynamics","volume":"58","author":"Reed","year":"2018","journal-title":"J. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13052-022-01361-z","article-title":"Drug dosing in children with obesity: A narrative updated review","volume":"48","author":"Gaeta","year":"2022","journal-title":"Ital. J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s40272-019-00352-8","article-title":"Drug Dose Selection in Pediatric Obesity: Available Information for the Most Commonly Prescribed Drugs to Children","volume":"21","author":"Kyler","year":"2019","journal-title":"Pediatr. Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/pan.12396","article-title":"A retrospective description of anesthetic medication dosing in overweight and obese children","volume":"24","author":"Burke","year":"2014","journal-title":"Pediatr. Anesth."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1002\/oby.22739","article-title":"Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review","volume":"28","author":"Ameer","year":"2020","journal-title":"Obesity"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"542","DOI":"10.2146\/ajhp140280","article-title":"Development of recommendations for dosing of commonly prescribed medications in critically ill obese children","volume":"72","author":"Ross","year":"2015","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.pcl.2017.08.011","article-title":"Drug Dosing in Obese Children: Challenges and Evidence-Based Strategies","volume":"64","author":"Xiong","year":"2017","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_17","unstructured":"Neonatal & Paediatric Pharmacy Group (2023, May 01). How Should Medicines Be Dosed in Children Who Are Obese?. Available online: https:\/\/nppg.org.uk\/wp-content\/uploads\/2024\/08\/UKMIQA-drug-dosing-in-childhood-obesity.pdf."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.clinthera.2015.08.006","article-title":"Best Pharmaceuticals for Children Act\u2014Pediatric Trials Network Administrative Core, C. Gaps in Drug Dosing for Obese Children: A Systematic Review of Commonly Prescribed Emergency Care Medications","volume":"37","author":"Rowe","year":"2015","journal-title":"Clin. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s40267-020-00734-w","article-title":"Dosage adjustment in obese children, even for common drugs, is largely unclear and a treat-to-effect approach may work best","volume":"36","author":"Writers","year":"2020","journal-title":"Drugs Ther. Perspect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/ACO.0000000000000991","article-title":"Pediatric obesity and perioperative medicine","volume":"34","author":"Mpody","year":"2021","journal-title":"Curr. Opin. Anesthesiol."},{"key":"ref_21","first-page":"94","article-title":"Pharmacokinetics and drug dosing in obese children","volume":"15","author":"Kendrick","year":"2010","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1016\/j.clinthera.2015.05.495","article-title":"Pediatric Obesity: Pharmacokinetics and Implications for Drug Dosing","volume":"37","author":"Kendrick","year":"2015","journal-title":"Clin. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1001\/jamapediatrics.2015.132","article-title":"Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review","volume":"169","author":"Hill","year":"2015","journal-title":"JAMA Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1080\/17425255.2022.2132931","article-title":"Drug pharmacokinetics in the obese population: Challenging common assumptions on predictors of obesity-related parameter changes","volume":"18","author":"Zhang","year":"2022","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/164_2019_250","article-title":"Pharmacokinetics and Pharmacodynamics of Drugs in Obese Pediatric Patients: How to Map Uncharted Clinical Territories","volume":"261","author":"Krekels","year":"2020","journal-title":"Pediatric Pharmacotherapy; Handbook of Experimental Pharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2022060640","DOI":"10.1542\/peds.2022-060640","article-title":"Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity","volume":"151","author":"Hampl","year":"2023","journal-title":"Pediatrics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S2213-8587(22)00047-X","article-title":"Obesity in children and adolescents: Epidemiology, causes, assessment, and management","volume":"10","author":"Jebeile","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100010","DOI":"10.1016\/j.obpill.2022.100010","article-title":"Assessment, differential diagnosis, and initial clinical evaluation of the pediatric patient with obesity: An Obesity Medical Association (OMA) Clinical Practice Statement 2022","volume":"1","author":"Cuda","year":"2022","journal-title":"Obes. Pillars"},{"key":"ref_29","unstructured":"World Health Organization (2025, January 01). Child Growth Standards. Available online: https:\/\/www.who.int\/tools\/child-growth-standards\/who-multicentre-growth-reference-study."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gerhart, J.G., Balevic, S., Sinha, J., Perrin, E.M., Wang, J., Edginton, A.N., and Gonzalez, D. (2022). Characterizing Pharmacokinetics in Children With Obesity-Physiological, Drug, Patient, and Methodological Considerations. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.818726"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1542\/peds.2012-0596","article-title":"Clinical tracking of severely obese children: A new growth chart","volume":"130","author":"Gulati","year":"2012","journal-title":"Pediatrics"},{"key":"ref_32","unstructured":"National Center for Health Statistics (2025, February 01). CDC Growth Charts, Available online: https:\/\/www.cdc.gov\/growthcharts\/cdc-growth-charts.htm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jpeds.2018.01.028","article-title":"Validity of Body Mass Index as a Measure of Adiposity in Infancy","volume":"196","author":"Bell","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e20153492","DOI":"10.1542\/peds.2015-3492","article-title":"Infant BMI or Weight-for-Length and Obesity Risk in Early Childhood","volume":"137","author":"Roy","year":"2016","journal-title":"Pediatrics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/s41430-023-01322-7","article-title":"Body composition from birth to 2 years","volume":"78","author":"Hills","year":"2024","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/ejcn.2015.117","article-title":"Body composition during fetal development and infancy through the age of 5 years","volume":"69","author":"Paley","year":"2015","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/sj.ijo.0803402","article-title":"Body composition in normal weight, overweight and obese children: Matched case-control analyses of total and regional tissue masses, and body composition trends in relation to relative weight","volume":"30","author":"Wells","year":"2006","journal-title":"Int. J. Obes."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1136\/adc.2009.163055","article-title":"Dosing dilemmas in obese children","volume":"95","author":"Mulla","year":"2010","journal-title":"Arch. Dis. Child. Educ. Pract. Ed."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1460-9592.2011.03788.x","article-title":"My child is unique; the pharmacokinetics are universal","volume":"22","author":"Anderson","year":"2012","journal-title":"Pediatr. Anesth."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Raes, A., Van Aken, S., Craen, M., Donckerwolcke, R., and Vande Walle, J. (2006). A reference frame for blood volume in children and adolescents. BMC Pediatr., 6.","DOI":"10.1186\/1471-2431-6-3"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/j.1365-2125.2011.04159.x","article-title":"Therapeutic drug monitoring to adjust dosing in morbid obesity\u2014A new use for an old methodology","volume":"73","author":"Martin","year":"2012","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.3928\/19382359-20230102-06","article-title":"Metabolic Consequences of Pediatric Obesity: A Review of Pathophysiology, Screening, and Treatment","volume":"52","author":"Gunaratne","year":"2023","journal-title":"Pediatr. Ann."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jia, S., Ye, X., Wu, T., Wang, Z., and Wu, J. (2025). Global prevalence of metabolic dysfunction-associated fatty liver disease in children and adolescents with overweight and obesity: A systematic review and meta-analysis. BMC Gastroenterol., 25.","DOI":"10.1186\/s12876-025-04314-y"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/bcp.15990","article-title":"Effect of changes in metabolic enzymes and transporters on drug metabolism in the context of liver disease: Impact on pharmacokinetics and drug-drug interactions","volume":"90","author":"Armani","year":"2024","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hertis Petek, T., Homsak, E., Svetej, M., and Marcun Varda, N. (2024). Systemic Inflammation and Oxidative Stress in Childhood Obesity: Sex Differences in Adiposity Indices and Cardiovascular Risk. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010058"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Umano, G.R., Pistone, C., Tondina, E., Moiraghi, A., Lauretta, D., Miraglia Del Giudice, E., and Brambilla, I. (2019). Pediatric Obesity and the Immune System. Front. Pediatr., 7.","DOI":"10.3389\/fped.2019.00487"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"a1435","DOI":"10.4102\/phcfm.v9i1.1435","article-title":"Obesity and kidney disease: Hidden consequences of the epidemic","volume":"9","author":"Kovesdy","year":"2017","journal-title":"Afr. J. Prim. Health Care Fam. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1007\/s00431-024-05641-0","article-title":"Kidney function evaluation in children and adolescents with obesity: A not-negligible need","volume":"183","author":"Barlaba","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s13052-025-02090-9","article-title":"Obesity-related kidney disease: A review on ultrasound applications","volume":"51","author":"Pucci","year":"2025","journal-title":"Ital. J. Pediatr."},{"key":"ref_50","unstructured":"Buxton, I. (2018). Farmacocin\u00e9tica: Din\u00e1mica de la absorci\u00f3n distribucion, metabolismo y eliminacion de f\u00e1rmacos. Goodman & Gilman\u2019s. The Pharmacological Basis of Therapeutics, McGRAW-HILL INTERAMERICANA EDITORES, S.A. de C.V.. [13th ed.]."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev-pharmtox-010814-124354","article-title":"Drug disposition in obesity: Toward evidence-based dosing","volume":"55","author":"Knibbe","year":"2015","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2165\/11599410-000000000-00000","article-title":"Impact of obesity on drug metabolism and elimination in adults and children","volume":"51","author":"Brill","year":"2012","journal-title":"Clin. Pharmacokinet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s11095-025-03885-5","article-title":"The Impact of Drug Properties and Severity of Obesity on Renal Drug Clearance Through Glomerular Filtration and Active Tubular Secretion: A Systematic Analysis Using PBPK Modeling","volume":"42","author":"Zhang","year":"2025","journal-title":"Pharm. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.anai.2018.05.001","article-title":"Epinephrine, auto-injectors, and anaphylaxis: Challenges of dose, depth, and device","volume":"121","author":"Brown","year":"2018","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"479","DOI":"10.5811\/westjem.2016.12.32279","article-title":"Skin to Intramuscular Compartment Thigh Measurement by Ultrasound in Pediatric Population","volume":"18","author":"Duong","year":"2017","journal-title":"West. J. Emerg. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/cei.12099","article-title":"Subcutaneous immunoglobulin (16 or 20%) therapy in obese patients with primary immunodeficiency: A retrospective analysis of administration by infusion pump or subcutaneous rapid push","volume":"173","author":"Shapiro","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_57","first-page":"81","article-title":"Medication Dosage in Overweight and Obese Children","volume":"22","author":"Matson","year":"2017","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e236","DOI":"10.1093\/pch\/pxaa108","article-title":"Prescribing drugs to overweight and obese children: Balancing efficacy and safety","volume":"26","author":"Roy","year":"2021","journal-title":"Paediatr. Child. Health"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1136\/archdischild-2013-303720","article-title":"Understanding dosing: Children are small adults, neonates are immature children","volume":"98","author":"Anderson","year":"2013","journal-title":"Arch. Dis. Child."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s40262-021-01072-4","article-title":"Development and Evaluation of a Virtual Population of Children with Obesity for Physiologically Based Pharmacokinetic Modeling","volume":"61","author":"Gerhart","year":"2022","journal-title":"Clin. Pharmacokinet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/jcph.1562","article-title":"Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis","volume":"60","author":"Maharaj","year":"2020","journal-title":"J. Clin. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/bcp.12693","article-title":"Population pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents","volume":"80","author":"Vaughns","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s40262-019-00838-1","article-title":"Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents","volume":"59","author":"Gade","year":"2020","journal-title":"Clin. Pharmacokinet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1111\/bcp.13602","article-title":"Higher chlorzoxazone clearance in obese children compared with nonobese peers","volume":"84","author":"Gade","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Anderson, B.J., and Cortinez, L.I. (2023). Perioperative Acetaminophen Dosing in Obese Children. Children, 10.","DOI":"10.3390\/children10040625"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/pan.13525","article-title":"Acetaminophen pharmacokinetics in severely obese adolescents and young adults","volume":"29","author":"Hakim","year":"2019","journal-title":"Pediatr. Anesth."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s40262-015-0357-0","article-title":"Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen","volume":"55","author":"Valitalo","year":"2016","journal-title":"Clin. Pharmacokinet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1365-2125.2011.03959.x","article-title":"Altered xanthine oxidase and N-acetyltransferase activity in obese children","volume":"72","author":"Chiney","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/00007691-199101000-00004","article-title":"Fat body mass and pharmacokinetics of oral 6-mercaptopurine in children with acute lymphoblastic leukemia","volume":"13","author":"Zuccaro","year":"1991","journal-title":"Ther. Drug Monit."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/MPG.0b013e3181f9b3a0","article-title":"Acetaminophen pharmacokinetics in children with nonalcoholic fatty liver disease","volume":"52","author":"Barshop","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.bbmt.2011.01.013","article-title":"Busulfan dosing in children with BMIs \u226585% undergoing HSCT: A new optimal strategy","volume":"17","author":"Browning","year":"2011","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"375","DOI":"10.2174\/157488612805076606","article-title":"Prospective evaluation of the dosing regimen of vancomycin in children of different weight categories","volume":"7","author":"Nassar","year":"2012","journal-title":"Curr. Drug Saf."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1007\/s00467-021-05396-y","article-title":"Creatinine-based GFR-estimating equations in children with overweight and obesity","volume":"37","author":"Pottel","year":"2022","journal-title":"Pediatr. Nephrol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1007\/s00467-022-05810-z","article-title":"Relation between obesity-related comorbidities and kidney function estimation in children","volume":"38","author":"Pottel","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/phar.1763","article-title":"Applicability of the Schwartz Equation and the Chronic Kidney Disease in Children Bedside Equation for Estimating Glomerular Filtration Rate in Overweight Children","volume":"36","author":"Lewis","year":"2016","journal-title":"Pharmacotherapy"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s00467-016-3367-8","article-title":"Normalization of glomerular filtration rate in obese children","volume":"31","author":"Schaefer","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00467-008-1064-y","article-title":"Effect of obesity on response to cardiovascular drugs in pediatric patients with renal disease","volume":"24","author":"Hanafy","year":"2009","journal-title":"Pediatr. Nephrol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/ijo.2012.62","article-title":"Obesity and the risk and outcome of infection","volume":"37","author":"Huttunen","year":"2013","journal-title":"Int. J. Obes."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.2165\/00003088-200645110-00003","article-title":"Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations","volume":"45","author":"Bartelink","year":"2006","journal-title":"Clin. Pharmacokinet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"S153","DOI":"10.1542\/peds.2012-0055I","article-title":"Standard 6: Age groups for pediatric trials","volume":"129","author":"Williams","year":"2012","journal-title":"Pediatrics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0022-3476(78)80601-5","article-title":"Geometric method for measuring body surface area: A height-weight formula validated in infants, children, and adults","volume":"93","author":"Haycock","year":"1978","journal-title":"J. Pediatr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1056\/NEJM198710223171717","article-title":"Simplified calculation of body-surface area","volume":"317","author":"Mosteller","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_83","first-page":"107","article-title":"Estimating ideal body mass in children","volume":"40","author":"Traub","year":"1983","journal-title":"Am. J. Hosp. Pharm."},{"key":"ref_84","first-page":"1514","article-title":"Estimating creatinine clearance in children: Comparison of three methods","volume":"37","author":"Rudd","year":"1980","journal-title":"Am. J. Hosp. Pharm."},{"key":"ref_85","first-page":"421","article-title":"Evaluation of Different Methods Used to Calculate Ideal Body Weight in the Pediatric Population","volume":"24","author":"Kang","year":"2019","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/anae.12860","article-title":"An aid to drug dosing safety in obese children: Development of a new nomogram and comparison with existing methods for estimation of ideal body weight and lean body mass","volume":"70","author":"Callaghan","year":"2015","journal-title":"Anaesthesia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.2165\/00003088-200544100-00004","article-title":"Quantification of lean bodyweight","volume":"44","author":"Janmahasatian","year":"2005","journal-title":"Clin. Pharmacokinet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s40262-015-0277-z","article-title":"Prediction of Fat-Free Mass in Children","volume":"54","author":"Goulding","year":"2015","journal-title":"Clin. Pharmacokinet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1111\/pan.13272","article-title":"What is the best size predictor for dose in the obese child?","volume":"27","author":"Anderson","year":"2017","journal-title":"Pediatr. Anesth."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"S59","DOI":"10.1016\/j.ejps.2017.05.056","article-title":"Allometric size: The scientific theory and extension to normal fat mass","volume":"109","author":"Holford","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1023\/A:1010639201787","article-title":"Body surface area as a determinant of pharmacokinetics and drug dosing","volume":"19","author":"Sawyer","year":"2001","journal-title":"Investig. New Drugs"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/j.1651-2227.2011.02580.x","article-title":"Estimation of body surface area in various childhood ages\u2014Validation of the Mosteller formula","volume":"101","author":"Lindemalm","year":"2012","journal-title":"Acta Paediatr."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1002\/j.1875-9114.2012.01108.x","article-title":"Drug dosing based on weight and body surface area: Mathematical assumptions and limitations in obese adults","volume":"32","author":"Pai","year":"2012","journal-title":"Pharmacotherapy"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"268","DOI":"10.4274\/jcrpe.galenos.2023.2022-12-18","article-title":"Growth Hormone Dosing Estimations Based on Body Weight Versus Body Surface Area","volume":"15","author":"Besci","year":"2023","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/cpt.2618","article-title":"Use of Real-World Data and Physiologically-Based Pharmacokinetic Modeling to Characterize Enoxaparin Disposition in Children With Obesity","volume":"112","author":"Gerhart","year":"2022","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5348","DOI":"10.1111\/bcp.15459","article-title":"Optimal dosing of enoxaparin in overweight and obese children","volume":"88","author":"Derbalah","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1097\/ALN.0000000000004115","article-title":"Allometric Scaling in Pharmacokinetic Studies in Anesthesiology","volume":"136","author":"Eleveld","year":"2022","journal-title":"Anesthesiology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1460-9592.2011.03536.x","article-title":"Tips and traps analyzing pediatric PK data","volume":"21","author":"Anderson","year":"2011","journal-title":"Pediatr. Anesth."},{"key":"ref_99","unstructured":"Holford, S.H.N. (2025, September 01). NextDose: A Web-Based Bayesian Dose Forecasting Tool. Available online: https:\/\/nextdose.org\/about."},{"key":"ref_100","unstructured":"Vancomycin Hydrochloride. MerativeTM Micromedex\u00ae DRUGDEX\u00ae (Electronic Version), Merative. Available online: https:\/\/www.micromedexsolutions.com\/."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/ajhp\/zxaa036","article-title":"Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists","volume":"77","author":"Rybak","year":"2020","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1365-2125.2004.02157.x","article-title":"What is the best size descriptor to use for pharmacokinetic studies in the obese?","volume":"58","author":"Green","year":"2004","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1093\/ajhp\/zxz161","article-title":"Pharmacokinetic considerations in pediatric pharmacotherapy","volume":"76","author":"Lim","year":"2019","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Simeoli, R., Dorlo, T.P.C., Hanff, L.M., Huitema, A.D.R., and Dreesen, E. (2022). Editorial: Therapeutic Drug Monitoring (TDM): A Useful Tool for Pediatric Pharmacology Applied to Routine Clinical Practice. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.931843"},{"key":"ref_105","unstructured":"Molina, E.V. (2011). Farmacocin\u00e9tica cl\u00ednica en pediatr\u00eda. Farmacia Pedi\u00e1trica Hospitalaria, Elsevier."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"809","DOI":"10.2165\/11594420-000000000-00000","article-title":"Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: Expected variations in clearance","volume":"50","author":"Ghobadi","year":"2011","journal-title":"Clin. Pharmacokinet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/clpt.2012.64","article-title":"Physiologically based pharmacokinetic (PBPK) modeling in children","volume":"92","author":"Barrett","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Burhanuddin, K., Mohammed, A., and Badhan, R.K.S. (2024). The Impact of Paediatric Obesity on Drug Pharmacokinetics: A Virtual Clinical Trials Case Study with Amlodipine. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16040489"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/164_2024_733","article-title":"What Is QSP and Why Does It Exist?: A Brief History","volume":"289","author":"Friedrich","year":"2025","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1002\/cpt.3049","article-title":"Machine Learning: A New Approach for Dose Individualization","volume":"115","author":"Li","year":"2024","journal-title":"Clin. Pharmacol. Ther."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/1\/16\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T07:06:32Z","timestamp":1766387192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/1\/16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,21]]},"references-count":110,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ph19010016"],"URL":"https:\/\/doi.org\/10.3390\/ph19010016","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,21]]}}}