vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v22i4.2593vsp-3262Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWДозирование лекарственных средств в педиатрии: возможные подходыDrug Dosing in Pediatrics: Possible Approacheshttps://orcid.org/0000-0002-1919-2909КолбинА. С.KolbinAlexey S.

Колбин Алексей Сергеевич - доктор медицинских наук, профессор, заведующий кафедрой клинической фармакологии и доказательной медицины ПСПбГМУ им. акад. И.П. Павлова; профессор кафедры фармакологии медицинского факультета СПбГУ.

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

тел.: +7 (812) 338-78-95

Saint Petersburg

alex.kolbin@mail.ruhttps://orcid.org/0000-0003-2121-094XРадаеваК. С.RadaevaKseniya S.

Санкт-Петербург

Saint Petersburg

Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова; Санкт-Петербургский государственный университетРоссияPavlov First Saint Petersburg State Medical University; Saint Petersburg UniversityRussian FederationПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияPavlov First Saint Petersburg State Medical UniversityRussian Federation202325082023224289297Copyright © Колбин А.С., Радаева К.С., 20232023Колбин А.С., Радаева К.С.Kolbin A.S., Radaeva K.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/3262

Дозирование лекарственных средств (ЛС) остается одной из важных проблем современной педиатрии. Недостаточное количество клинических исследований, уязвимые популяции пациентов (недоношенные новорожденные, пациенты с почечной и/или печеночной недостаточностью, дети с избыточной массой тела) и высокий риск полипрагмазии создают дополнительные сложности для практикующих врачей. В настоящем обзоре представлено описание используемых в настоящее время подходов к дозированию ЛС у детей. Показано, что для решения проблем дозирования ЛС принято использовать прогностические модели, учитывающие особенности пациентов младшего возраста. В их числе модели, основанные на физиологии фармакокинетического масштабирования, на данных популяционной фармакокинетики, реальной клинической практики и фармакогенетического тестирования, а также дозирование, основанное на результатах моделирования и симуляции. При этом используют информацию доклинических и клинических исследований с одной или несколькими фармакостатистическими моделями.

Drug dosing remains one of the topical issues of modern pediatrics. Insufficient number of clinical studies, vulnerable patient populations (preterm newborns, patients with renal and/or hepatic insufficiency, obesity), and high risk of polypragmasy create additional difficulties for practicing physicians. This review provides description of currently used approaches to drugs dosing in children. It has been shown that prognostic models should be used for solving drugs dosing issues regarding characteristics of young patients. Such models include: physiologically based pharmacokinetic modelling; population pharmacokinetic analysis; model-based precision dosing; modeling and simulation approach; use of real world data; and pharmacogenetic testing-based dosing. These models use information from preclinical and clinical stu

детидозированиелекарственные средствапопуляционная фармакокинетикафизиологически обоснованная фармакокинетическая модельклинические исследованияразработка лекарствchildrendosingmedicationspopulation pharmacokineticsphysiologically based pharmacokinetic modelclinical studiesdrug designОтсутствует.Not specified.ReferencesICH Harmonised Guideline Pediatric Extrapolation E11A ICH Consensus Guideline. 2022. Available online: https://www.ema.europa.eu/en/documents/scientific-guideline/draft-ich-guideline-e11a-pediatric-extrapolation-step-2b_en.pdf. Accessed on July 22, 2023.ICH Harmonised Guideline Pediatric Extrapolation E11A ICH Consensus Guideline. 2022. Available online: https://www.ema.europa.eu/en/documents/scientific-guideline/draft-ich-guideline-e11a-pediatric-extrapolation-step-2b_en.pdf. Accessed on July 22, 2023.Food and Drug Administration Modernization Act of 1997: Text S.830. 105th Congress (1997-1998). In: Congress.gov. Available online: https://www.congress.gov/bill/105th-congress/senate-bill/830/text. Accessed on July 22, 2023.Food and Drug Administration Modernization Act of 1997: Text S.830. 105th Congress (1997-1998). In: Congress.gov. Available online: https://www.congress.gov/bill/105th-congress/senate-bill/830/text. Accessed on July 22, 2023.Колбин А.С. Клиническая фармакология для педиатров: учебное пособие. — М.: ГЭОТАР-Медиа; 2020. — 288 с.Kolbin AS. Klinicheskaya farmakologiya dlya pediatrov: Tutorial. Moscow: GEOTAR-Media; 2020. 288 p. (In Russ).The European Agency for the Evaluation of Medicinal Products, Human Evaluations Unit. Report on the experts round table on the difficulties related to the use of new medicinal products in children held on 18 December 1997. EMEA/27164/98 Rev. 1. London, 30 July 1998. Available online: https://www.ema.europa.eu/en/documents/report/report-experts-round-table-difficulties-related-use-new-medicinal-products-children-held-18-december_en.pdf. Accessed on July 22, 2023.The European Agency for the Evaluation of Medicinal Products, Human Evaluations Unit. Report on the experts round table on the difficulties related to the use of new medicinal products in children held on 18 December 1997. EMEA/27164/98 Rev. 1. London, 30 July 1998. Available online: https://www.ema.europa.eu/en/documents/report/report-experts-round-table-difficulties-related-use-new-medicinal-products-children-held-18-december_en.pdf. Accessed on July 22, 2023.Best Pharmaceuticals for Children Act. Summary: Text S.3452. 107th Congress (2001-2002). In: Congress.gov. Available online: https://www.congress.gov/bill/107th-congress/senate-bill/1789/text. Accessed on July 22, 2023.Best Pharmaceuticals for Children Act. Summary: Text S.3452. 107th Congress (2001-2002). In: Congress.gov. Available online: https://www.congress.gov/bill/107th-congress/senate-bill/1789/text. Accessed on July 22, 2023.Pediatric Research Equity Act of 2003: Text S.650. 108th Congress (2003-2004). In: Congress.gov. Available online: https://www.congress.gov/bill/108th-congress/senate-bill/650/text. Accessed on July 22, 2023.Pediatric Research Equity Act of 2003: Text S.650. 108th Congress (2003-2004). In: Congress.gov. Available online: https://www.congress.gov/bill/108th-congress/senate-bill/650/text. Accessed on July 22, 2023.Намазова-Баранова Л.С., Садеки Н., Баранов А.А. Открытые вопросы клинических исследований с участием детей в качестве субъектов исследования: обзор литературы. Педиатрическая фармакология. 2022;19(1):61-71. https://doi.org/10.15690/10.15690/pf.v19i1.2375Namazova-Baranova L.S., Sadeqi N., Baranov A.A. Unanswered Questions in Pediatric Clinical Trials: Literature Review. Pediatric pharmacology. 2022;19(1):61-71. (In Russ.) https://doi.org/10.15690/10.15690/pf.v19i1.2375Завидова С., Намазова-Баранова Л., Тополянская С. Клинические исследования лекарственных препаратов в педиатрии: проблемы и достижения. Педиатрическая фармакология. 2010; 7(1):6-14.Zavidova S., Namazova-Baranova L., Topolyanskaya S. CLINICAL TRIALS OF DRUGS IN PEDIATRICS: PROBLEMS AND ACHIEVEMENTS. Pediatric pharmacology. 2010;7(1):6-14.Burckart GJ, van den Anker JN. Neonatal and Pediatric Dose Selection: Quo Vadis? J Clin Pharmacol. 2021;61(Suppl 1):S7-S8. doi: https://doi.org/10.1002/jcph.1888Burckart GJ, van den Anker JN. Neonatal and Pediatric Dose Selection: Quo Vadis? J Clin Pharmacol. 2021;61(Suppl 1):S7-S8. doi: https://doi.org/10.1002/jcph.1888Powell JR, Cook J, Wang Y, et al. Drug Dosing Recommendations for All Patients: A Roadmap for Change. Clin Pharmacol Ther. 2021;109(1):65-72. doi: https://doi.org/10.1002/cpt.1923Powell JR, Cook J, Wang Y, et al. Drug Dosing Recommendations for All Patients: A Roadmap for Change. Clin Pharmacol Ther. 2021;109(1):65-72. doi: https://doi.org/10.1002/cpt.1923Elias GP, Antoniali C, Mariano RC. Comparative study of rules employed for calculation of pediatric drug dosage. J Appl Oral Sci. 2005;13(2):114-119. doi: https://doi.org/10.1590/s1678-77572005000200004Elias GP, Antoniali C, Mariano RC. Comparative study of rules employed for calculation of pediatric drug dosage. J Appl Oral Sci. 2005;13(2):114-119. doi: https://doi.org/10.1590/s1678-77572005000200004van Rongen A, Krekels EH, Calvier EA, et al. An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables. Expert Opin Drug Metab Toxicol. 2022;18(2):99-113. doi: https://doi.org/10.1080/17425255.2021.2027907van Rongen A, Krekels EH, Calvier EA, et al. An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables. Expert Opin Drug Metab Toxicol. 2022;18(2):99-113. doi: https://doi.org/10.1080/17425255.2021.2027907Momper JD, Mulugeta Y, Green DJ, et al. Adolescent dosing and labeling since the Food and Drug Administration Amendments Act of 2007. JAMA Pediatr. 2013;167(10):926-932. doi: https://doi.org/10.1001/jamapediatrics.2013.465Momper JD, Mulugeta Y, Green DJ, et al. Adolescent dosing and labeling since the Food and Drug Administration Amendments Act of 2007. JAMA Pediatr. 2013;167(10):926-932. doi: https://doi.org/10.1001/jamapediatrics.2013.465Tegenge MA, Mahmood I. Age- and Bodyweight-dependent Allometric Exponent Model for Scaling Clearance and Maintenance Dose of Theophylline From Neonates to Adults. Ther Drug Monit. 2018;40(5):635-641. doi: https://doi.org/10.1097/FTD.0000000000000543Tegenge MA, Mahmood I. Age- and Bodyweight-dependent Allometric Exponent Model for Scaling Clearance and Maintenance Dose of Theophylline From Neonates to Adults. Ther Drug Monit. 2018;40(5):635-641. doi: https://doi.org/10.1097/FTD.0000000000000543Holford N. Dosing in children. Clin Pharmacol Ther. 2010; 87(3):367-370. doi: https://doi.org/10.1038/clpt.2009.262Holford N. Dosing in children. Clin Pharmacol Ther. 2010; 87(3):367-370. doi: https://doi.org/10.1038/clpt.2009.262Johnson TN, Ke AB. Physiologically Based Pharmacokinetic Modeling and Allometric Scaling in Pediatric Drug Development: Where Do We Draw the Line? J Clin Pharmacol. 2021;61 (Suppl 1):S83-S93. doi: https://doi.org/10.1002/jcph.1834Johnson TN, Ke AB. Physiologically Based Pharmacokinetic Modeling and Allometric Scaling in Pediatric Drug Development: Where Do We Draw the Line? J Clin Pharmacol. 2021;61 (Suppl 1):S83-S93. doi: https://doi.org/10.1002/jcph.1834Calvier EA, Krekels EH, Valitalo PA, et al. Allometric Scaling of Clearance in Paediatric Patients: When Does the Magic of 0.75 Fade? Clin Pharmacokinet. 2017;56(3):273-285. doi: https://doi.org/10.1007/s40262-016-0436-xCalvier EA, Krekels EH, Valitalo PA, et al. Allometric Scaling of Clearance in Paediatric Patients: When Does the Magic of 0.75 Fade? Clin Pharmacokinet. 2017;56(3):273-285. doi: https://doi.org/10.1007/s40262-016-0436-xMalik PRV, Temrikar ZH, Chelle P, et al. Pediatric Dose Selection for Therapeutic Proteins. J Clin Pharmacol. 2021;61(Suppl 1): S193-S206. doi: https://doi.org/10.1002/jcph.1829Malik PRV, Temrikar ZH, Chelle P, et al. Pediatric Dose Selection for Therapeutic Proteins. J Clin Pharmacol. 2021;61(Suppl 1): S193-S206. doi: https://doi.org/10.1002/jcph.1829Mahmood I, Tegenge MA. Spreadsheet-Based Minimal Physiological Models for the Prediction of Clearance of Therapeutic Proteins in Pediatric Patients. J Clin Pharmacol. 2021;61 (Suppl 1):S108-S116. doi: https://doi.org/10.1002/jcph.1846Mahmood I, Tegenge MA. Spreadsheet-Based Minimal Physiological Models for the Prediction of Clearance of Therapeutic Proteins in Pediatric Patients. J Clin Pharmacol. 2021;61 (Suppl 1):S108-S116. doi: https://doi.org/10.1002/jcph.1846Perry C, Davis G, Conner TM, Zhang T. Utilization of Physiologically Based Pharmacokinetic Modeling in Clinical Pharmacology and Therapeutics: an Overview. Curr Pharmacol Rep. 2020;6(3):71-84. doi: https://doi.org/10.1007/s40495-020-00212-xPerry C, Davis G, Conner TM, Zhang T. Utilization of Physiologically Based Pharmacokinetic Modeling in Clinical Pharmacology and Therapeutics: an Overview. Curr Pharmacol Rep. 2020;6(3):71-84. doi: https://doi.org/10.1007/s40495-020-00212-xSalerno SN, Edginton A, Gerhart JG, et al. Physiologically-based pharmacokinetic modeling characterizes the CYP3A-mediated drug-drug interaction between fluconazole and sildenafil in infants. Clin Pharmacol Ther. 2021;109(1):253-262. doi: https://doi.org/10.1002/cpt.1990Salerno SN, Edginton A, Gerhart JG, et al. Physiologically-based pharmacokinetic modeling characterizes the CYP3A-mediated drug-drug interaction between fluconazole and sildenafil in infants. Clin Pharmacol Ther. 2021;109(1):253-262. doi: https://doi.org/10.1002/cpt.1990Grimstein M, Yang Y, Zhang X, et al. Physiologically Based Pharmacokinetic Modeling in Regulatory Science: An Update From the U.S. Food and Drug Administration's Office of Clinical Pharmacology. J Pharm Sci. 2019;108(1):21-25. doi: https://doi.org/10.1016/j.xphs.2018.10.033Grimstein M, Yang Y, Zhang X, et al. Physiologically Based Pharmacokinetic Modeling in Regulatory Science: An Update From the U.S. Food and Drug Administration's Office of Clinical Pharmacology. J Pharm Sci. 2019;108(1):21-25. doi: https://doi.org/10.1016/j.xphs.2018.10.033Gonzalez D, Sinha J. Pediatric Drug-Drug Interaction Evaluation: Drug, Patient Population, and Methodological Considerations. J Clin Pharmacol. 2021;61(Suppl 1):S175-S187. doi: https://doi.org/10.1002/jcph.1881Gonzalez D, Sinha J. Pediatric Drug-Drug Interaction Evaluation: Drug, Patient Population, and Methodological Considerations. J Clin Pharmacol. 2021;61(Suppl 1):S175-S187. doi: https://doi.org/10.1002/jcph.1881Smits A, Kulo A, van den Anker J, Allegaert K. The amikacin research program: a stepwise approach to validate dosing regimens in neonates. Exp Opin Drug Metabol Toxicol. 2017;13(2):157-166. doi: https://doi.org/10.1080/17425255.2017.1234606Smits A, Kulo A, van den Anker J, Allegaert K. The amikacin research program: a stepwise approach to validate dosing regimens in neonates. Exp Opin Drug Metabol Toxicol. 2017;13(2):157-166. doi: https://doi.org/10.1080/17425255.2017.1234606Kalaria SN, Farchione TR, Uppoor R, et al. Extrapolation of Efficacy and Dose Selection in Pediatrics: A Case Example of Atypical Antipsychotics in Adolescents With Schizophrenia and Bipolar I Disorder. J Clin Pharmacol. 2021;61(Suppl 1):S117-S124. doi: https://doi.org/10.1002/jcph.1836Kalaria SN, Farchione TR, Uppoor R, et al. Extrapolation of Efficacy and Dose Selection in Pediatrics: A Case Example of Atypical Antipsychotics in Adolescents With Schizophrenia and Bipolar I Disorder. J Clin Pharmacol. 2021;61(Suppl 1):S117-S124. doi: https://doi.org/10.1002/jcph.1836Тихов М.С., Шкилева К.Н. Модифицированный метод оценивания Рида и Менча в зависимости доза-эффект // Вестник Тверского государственного университета. Серия: Прикладная математика. — 2019. — № 4. — С. 5-26. — doi: https://doi.org/10.26456/vtpmk543Tikhov MS, Shkileva KN. A modified Reed- Muench method of estimation in dose-effect relationship. Vestnik TvGU. Seriya: Prikladnaya Matematika = Herald of Tver State University Series: Applied Mathematics. 2019;(4):5-26. (In Russ). doi: https://doi.org/10.26456/vtpmk543Khurana M. Renal Impairment in Pediatric Patients: Current Approaches to Drug Dosing. J Clin Pharmacol. 2021;61(Suppl 1): S161-S164. doi: https://doi.org/10.1002/jcph.1908Khurana M. Renal Impairment in Pediatric Patients: Current Approaches to Drug Dosing. J Clin Pharmacol. 2021;61(Suppl 1): S161-S164. doi: https://doi.org/10.1002/jcph.1908Zhang Q, Travis J, Rothwell R, et al. Applying the Noninferiority Paradigm to Assess Exposure-Response Similarity and Dose Between Pediatric and Adult Patients. J Clin Pharmacol. 2021;61(S1): S165-S174. doi: https://doi.org/10.1002/jcph.1885Zhang Q, Travis J, Rothwell R, et al. Applying the Noninferiority Paradigm to Assess Exposure-Response Similarity and Dose Between Pediatric and Adult Patients. J Clin Pharmacol. 2021;61(S1): S165-S174. doi: https://doi.org/10.1002/jcph.1885Ramsey LB, Brown JT, Vear SI, et al. Gene-Based Dose Optimization in Children. Annu Rev Pharmacol Toxicol. 2020;60:311-331. doi: https://doi.org/10.1146/annurev-pharmtox-010919-023459Ramsey LB, Brown JT, Vear SI, et al. Gene-Based Dose Optimiza-tion in Children. Annu Rev Pharmacol Toxicol. 2020;60:311-331. doi: https://doi.org/10.1146/annurev-pharmtox-010919-023459Hoshitsuki K, Fernandez CA, Yang JJ. Pharmacogenomics for Drug Dosing in Children: Current Use, Knowledge, and Gaps. J Clin Pharmacol. 2021;61(S1):S188-S192. doi: https://doi.org/10.1002/jcph.1891Hoshitsuki K, Fernandez CA, Yang JJ. Pharmacogenomics for Drug Dosing in Children: Current Use, Knowledge, and Gaps. J Clin Pharmacol. 2021;61(S1):S188-S192. doi: https://doi.org/10.1002/jcph.1891Relling MV, Pui CH, Cheng C, Evans WE. Thiopurine methyltrans-ferase in acute lymphoblastic leukemia. Blood. 2006;107(2): 843-844. doi: https://doi.org/10.1182/blood-2005-08-3379Relling MV, Pui CH, Cheng C, Evans WE. Thiopurine methyltrans-ferase in acute lymphoblastic leukemia. Blood. 2006;107(2): 843-844. doi: https://doi.org/10.1182/blood-2005-08-3379Hahn D, Fukuda T, Euteneuer JC, et al. Influence of MRP3 Genetics and Hepatic Expression Ontogeny for Morphine Disposition in Neonatal and Pediatric Patients. J Clin Pharmacol. 2020;60(8): 992-998. doi: https://doi.org/10.1002/jcph.1592Hahn D, Fukuda T, Euteneuer JC, et al. Influence of MRP3 Genetics and Hepatic Expression Ontogeny for Morphine Disposition in Neonatal and Pediatric Patients. J Clin Pharmacol. 2020;60(8): 992-998. doi: https://doi.org/10.1002/jcph.1592Ward RM, Tammara B, Sullivan SE, et al. Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD). Eur J Clin Pharmacol. 2010;66(6):555-561. doi: https://doi.org/10.1007/s00228-010-0811-8Ward RM, Tammara B, Sullivan SE, et al. Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD). Eur J Clin Pharmacol. 2010;66(6):555-561. doi: https://doi.org/10.1007/s00228-010-0811-8Хохлов А.Л., Сычев Д.А. Концепция пациентоориентированности в медицине и фармации // Пациентоориентированная медицина и фармация. — 2023. — Т. 1. — № 1. — С. 1-4. — doi: https://doi.org/10.37489/2949-1924-0001Khokhlov AL, Sychev DA. The concept of patient-oriented medicine and pharmacy. Patient-Oriented Medicine and Pharmacy. 2023;1(1):1-4. (In Russ). doi: https://doi.org/10.37489/2949-1924-0001Решение Совета ЕЭК от 17 марта 2022 г. № 36 «О внесении изменений в Правила регистрации и экспертизы лекарственных средств для медицинского применения».Decision of the Eurasian Economic Commission Council dated March 17, 2022 No. 36 “O vnesenii izmenenii v Pravila registratsii i ekspertizy lekarstvennykh sredstv dlya meditsinskogo primeneniya”. (In Russ).Barrett JS, Barrett RF, Vinks AA. Status Toward the Implementation of Precision Dosing in Children. J Clin Pharmacol. 2021; 61(Suppl1):S36-S51. doi: https://doi.org/10.1002/jcph.1830Barrett JS, Barrett RF, Vinks AA. Status Toward the Implementation of Precision Dosing in Children. J Clin Pharmacol. 2021; 61(Suppl1):S36-S51. doi: https://doi.org/10.1002/jcph.1830Jarugula P, Scott S, Ivaturi V, et al. Understanding the Role of Pharmacometrics-Based Clinical Decision Support Systems in Pediatric Patient Management: A Case Study Using Lyv Software. J Clin Pharmacol. 2021;61(Suppl 1):S125-S132. doi: https://doi.org/10.1002/jcph.1892Jarugula P, Scott S, Ivaturi V, et al. Understanding the Role of Pharmacometrics-Based Clinical Decision Support Systems in Pediatric Patient Management: A Case Study Using Lyv Software. J Clin Pharmacol. 2021;61(Suppl 1):S125-S132. doi: https://doi.org/10.1002/jcph.1892Колбин А.С., Белоусов Д.Ю., Зырянов С.К. и др. Исследования реальной клинической практики / под ред. А.С. Колбина. — М.: Издательство ОКИ; Буки Веди; 2020. — 208 с.Kolbin AS, Belousov D.Yu, Zyryanov SK, et al. Issledovaniya real'noi klinicheskoi praktiki. Kolbin AS, ed. Moscow: Izdatel'stvo OKI; Buki Vedi; 2020. 208 p. (In Russ).Гусев А.В., Зингерман Б.В., Тюфилин Д.С., Зинченко В.В. Электронные медицинские карты как источник данных реальной клинической практики // Реальная клиническая практика: данные и доказательства. — 2022. — Т. 2. — № 2. — С. 8-20. — doi: https://doi.org/10.37489/2782-3784-myrwd-13Gusev AV, Zingerman BV, Tyufilin DS, Zinchenko VV. Electronic medical records as a source of real-world clinical data. Real-World Data & Evidence. 2022;2(2):8-20. (In Russ). doi: https://doi.org/10.37489/2782-3784-myrwd-13van den Anker J, Allegaert K. Considerations for Drug Dosing in Premature Infants. J Clin Pharmacol. 2021;61(Suppl 1): S141-S151. doi: https://doi.org/10.1002/jcph.1884.van den Anker J, Allegaert K. Considerations for Drug Dosing in Premature Infants. J Clin Pharmacol. 2021;61(Suppl 1): S141-S151. doi: https://doi.org/10.1002/jcph.1884.Green FG, Park K, Burckart GJ. Methods Used for Pediatric Dose Selection in Drug Development Programs Submitted to the US FDA 2012-2020. J Clin Pharmacol. 2021;61(Suppl 1):S28-S35. doi: https://doi.org/10.1002/jcph.1853Green FG, Park K, Burckart GJ. Methods Used for Pediatric Dose Selection in Drug Development Programs Submitted to the US FDA 2012-2020. J Clin Pharmacol. 2021;61(Suppl 1):S28-S35. doi: https://doi.org/10.1002/jcph.1853Vinks AA, Barrett JS. Model-Informed Pediatric Drug Development: Application of Pharmacometrics to Define the Right Dose for Children. J Clin Pharmacol. 2021;61(Suppl 1):S52-S59. doi: https://doi.org/10.1002/jcph.1841Vinks AA, Barrett JS. Model-Informed Pediatric Drug Development: Application of Pharmacometrics to Define the Right Dose for Children. J Clin Pharmacol. 2021;61(Suppl 1):S52-S59. doi: https://doi.org/10.1002/jcph.1841

The authors declare that there are no conflicts of interest present.