Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling

For children, a special population who are continuously developing, a reasonable dosing strategy is the key to clinical therapy. Accurate dose predictions can help maximize efficacy and minimize pain in pediatrics. <b>Methods:</b> This study collected amlodipine pharmacokinetics (PK) dat...

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Autores principales:	Xiaolu Han, Xiaoxuan Hong, Xianfu Li, Yuxi Wang, Zengming Wang, Aiping Zheng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	amlodipine pediatric preparations dosage optimization PBPK model hypertension model-informed drug development Pediatrics RJ1-570
Acceso en línea:	https://doaj.org/article/1bff174e425343709d687d318bca480f
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spelling	oai:doaj.org-article:1bff174e425343709d687d318bca480f2021-11-25T17:13:50ZOptimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling10.3390/children81109502227-9067https://doaj.org/article/1bff174e425343709d687d318bca480f2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9067/8/11/950https://doaj.org/toc/2227-9067For children, a special population who are continuously developing, a reasonable dosing strategy is the key to clinical therapy. Accurate dose predictions can help maximize efficacy and minimize pain in pediatrics. <b>Methods:</b> This study collected amlodipine pharmacokinetics (PK) data from 236 Chinese male adults and established a physiological pharmacokinetic (PBPK) model for adults using GastroPlus™. A PBPK model of pediatrics is constructed based on hepatic-to-body size and enzyme metabolism, used similar to the AUC<sub>0-∞</sub> to deduce the optimal dosage of amlodipine for children aged 1–16 years. A curve of continuous administration for 2-, 6-, 12-, 16-, and 25-year-olds and a personalized administration program for 6-year-olds were developed. <b>Results:</b> The results show that children could not establish uniform allometric amplification rules. The optimal doses were 0.10 mg·kg<sup>−1</sup> for ages 2–6 years and −0.0028 × Age + 0.1148 (mg/kg) for ages 7–16 years, r = 0.9941. The trend for continuous administration was consistent among different groups. In a 6-year-old child, a maintenance dose of 2.30 mg was used to increase the initial dose by 2.00 mg and the treatment dose by 1.00 mg to maintain stable plasma concentrations. <b>Conclusions:</b> A PBPK model based on enzyme metabolism can accurately predict the changes in the pharmacokinetic parameters of amlodipine in pediatrics. It can be used to support the optimization of clinical treatment plans in pediatrics.Xiaolu HanXiaoxuan HongXianfu LiYuxi WangZengming WangAiping ZhengMDPI AGarticleamlodipinepediatric preparationsdosage optimizationPBPK modelhypertensionmodel-informed drug developmentPediatricsRJ1-570ENChildren, Vol 8, Iss 950, p 950 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amlodipine pediatric preparations dosage optimization PBPK model hypertension model-informed drug development Pediatrics RJ1-570
spellingShingle	amlodipine pediatric preparations dosage optimization PBPK model hypertension model-informed drug development Pediatrics RJ1-570 Xiaolu Han Xiaoxuan Hong Xianfu Li Yuxi Wang Zengming Wang Aiping Zheng Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling
description	For children, a special population who are continuously developing, a reasonable dosing strategy is the key to clinical therapy. Accurate dose predictions can help maximize efficacy and minimize pain in pediatrics. <b>Methods:</b> This study collected amlodipine pharmacokinetics (PK) data from 236 Chinese male adults and established a physiological pharmacokinetic (PBPK) model for adults using GastroPlus™. A PBPK model of pediatrics is constructed based on hepatic-to-body size and enzyme metabolism, used similar to the AUC<sub>0-∞</sub> to deduce the optimal dosage of amlodipine for children aged 1–16 years. A curve of continuous administration for 2-, 6-, 12-, 16-, and 25-year-olds and a personalized administration program for 6-year-olds were developed. <b>Results:</b> The results show that children could not establish uniform allometric amplification rules. The optimal doses were 0.10 mg·kg<sup>−1</sup> for ages 2–6 years and −0.0028 × Age + 0.1148 (mg/kg) for ages 7–16 years, r = 0.9941. The trend for continuous administration was consistent among different groups. In a 6-year-old child, a maintenance dose of 2.30 mg was used to increase the initial dose by 2.00 mg and the treatment dose by 1.00 mg to maintain stable plasma concentrations. <b>Conclusions:</b> A PBPK model based on enzyme metabolism can accurately predict the changes in the pharmacokinetic parameters of amlodipine in pediatrics. It can be used to support the optimization of clinical treatment plans in pediatrics.
format	article
author	Xiaolu Han Xiaoxuan Hong Xianfu Li Yuxi Wang Zengming Wang Aiping Zheng
author_facet	Xiaolu Han Xiaoxuan Hong Xianfu Li Yuxi Wang Zengming Wang Aiping Zheng
author_sort	Xiaolu Han
title	Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling
title_short	Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling
title_full	Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling
title_fullStr	Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling
title_full_unstemmed	Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling
title_sort	optimization of personalized amlodipine dosing strategies for children based on pharmacokinetic data from chinese male adults and pbpk modeling
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1bff174e425343709d687d318bca480f
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_version_	1718412574689591296

Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling

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