Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients

Traditionally, dosage for pediatric patients has been optimized using simple weight-scaled methods, but these methods do not always meet the requirements of children. To overcome this discrepancy, population pharmacokinetic (PK) modeling of size and maturation functions has been proposed. The main o...

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Main Authors: Hyun-moon Back, Jong Bong Lee, Nayoung Han, Sungwoo Goo, Eben Jung, Junyeong Kim, Byungjeong Song, Sook Hee An, Jung Tae Kim, Sandy Jeong Rhie, Yoon Sun Ree, Jung-woo Chae, JaeWoo Kim, Hwi-yeol Yun
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/11/6/259
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spelling doaj-7762106d76ec4058a9a84e37e59e0ecc2020-11-25T01:12:18ZengMDPI AGPharmaceutics1999-49232019-06-0111625910.3390/pharmaceutics11060259pharmaceutics11060259Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric PatientsHyun-moon Back0Jong Bong Lee1Nayoung Han2Sungwoo Goo3Eben Jung4Junyeong Kim5Byungjeong Song6Sook Hee An7Jung Tae Kim8Sandy Jeong Rhie9Yoon Sun Ree10Jung-woo Chae11JaeWoo Kim12Hwi-yeol Yun13Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USADepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USACollege of Pharmacy, Seoul National University, Gwanak-ro 1, Gwanakgu, Seoul 08826, KoreaCollege of Pharmacy, Chungnam National University, Daehak-ro 99, Yuseonggu, Daejeon 34134, KoreaMinistry of Food and Drug Safety, Osongsangmyung 2-ro 187, Cheongju, Chungbuk 28159, KoreaCollege of Pharmacy, Chungnam National University, Daehak-ro 99, Yuseonggu, Daejeon 34134, KoreaJW Pharmaceutical Corp., Drug Discovery Center, Nambusunhwan-ro 2477, Seochogu, Seoul 06725, KoreaCollege of Pharmacy, Wonkwang University, Iksandae-ro 460, Iksan, Jeonbuk 54538, KoreaDepartment of Pharmacy, Kyunghee University Hospital at Gang-dong, Dongnam-ro 892, Kangdonggu, Seoul 05278, KoreaCollege of Pharmacy, Ewha Womans University, Ewhayeodae-gil 52, Seoul 03760, KoreaDepartment of Pharmacy, Yonsei University Health System, Yonsei-ro 50-1, Seodaemun-gu, Seoul 03722, KoreaCollege of Pharmacy, Chungnam National University, Daehak-ro 99, Yuseonggu, Daejeon 34134, KoreaYangji Hospital, 1636 Nambusunhwan-ro, Gwanak-gu, Seoul 08779, KoreaCollege of Pharmacy, Chungnam National University, Daehak-ro 99, Yuseonggu, Daejeon 34134, KoreaTraditionally, dosage for pediatric patients has been optimized using simple weight-scaled methods, but these methods do not always meet the requirements of children. To overcome this discrepancy, population pharmacokinetic (PK) modeling of size and maturation functions has been proposed. The main objective of the present study was to evaluate a new modeling method for pediatric patients using clinical data from three different clinical studies. To develop the PK models, a nonlinear mixed effect modeling method was employed, and to explore PK differences in pediatric patients, size with allometric and maturation with Michaelis−Menten type functions were evaluated. Goodness of fit plots, visual predictive check and bootstrap were used for model evaluation. Single application of size scaling to PK parameters was statistically significant for the over one year old group. On the other hand, simultaneous use of size and maturation functions was statistically significant for infants younger than one year old. In conclusion, population PK modeling for pediatric patients was successfully performed using clinical data. Size and maturation functions were applied according to established criteria, and single use of size function was applicable for over one year ages, while size and maturation functions were more effective for PK analysis of neonates and infants.https://www.mdpi.com/1999-4923/11/6/259size functionmaturation functionpharmacometricspediatricscyclosporinphenobarbitalvancomycin
collection DOAJ
language English
format Article
sources DOAJ
author Hyun-moon Back
Jong Bong Lee
Nayoung Han
Sungwoo Goo
Eben Jung
Junyeong Kim
Byungjeong Song
Sook Hee An
Jung Tae Kim
Sandy Jeong Rhie
Yoon Sun Ree
Jung-woo Chae
JaeWoo Kim
Hwi-yeol Yun
spellingShingle Hyun-moon Back
Jong Bong Lee
Nayoung Han
Sungwoo Goo
Eben Jung
Junyeong Kim
Byungjeong Song
Sook Hee An
Jung Tae Kim
Sandy Jeong Rhie
Yoon Sun Ree
Jung-woo Chae
JaeWoo Kim
Hwi-yeol Yun
Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients
Pharmaceutics
size function
maturation function
pharmacometrics
pediatrics
cyclosporin
phenobarbital
vancomycin
author_facet Hyun-moon Back
Jong Bong Lee
Nayoung Han
Sungwoo Goo
Eben Jung
Junyeong Kim
Byungjeong Song
Sook Hee An
Jung Tae Kim
Sandy Jeong Rhie
Yoon Sun Ree
Jung-woo Chae
JaeWoo Kim
Hwi-yeol Yun
author_sort Hyun-moon Back
title Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients
title_short Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients
title_full Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients
title_fullStr Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients
title_full_unstemmed Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients
title_sort application of size and maturation functions to population pharmacokinetic modeling of pediatric patients
publisher MDPI AG
series Pharmaceutics
issn 1999-4923
publishDate 2019-06-01
description Traditionally, dosage for pediatric patients has been optimized using simple weight-scaled methods, but these methods do not always meet the requirements of children. To overcome this discrepancy, population pharmacokinetic (PK) modeling of size and maturation functions has been proposed. The main objective of the present study was to evaluate a new modeling method for pediatric patients using clinical data from three different clinical studies. To develop the PK models, a nonlinear mixed effect modeling method was employed, and to explore PK differences in pediatric patients, size with allometric and maturation with Michaelis−Menten type functions were evaluated. Goodness of fit plots, visual predictive check and bootstrap were used for model evaluation. Single application of size scaling to PK parameters was statistically significant for the over one year old group. On the other hand, simultaneous use of size and maturation functions was statistically significant for infants younger than one year old. In conclusion, population PK modeling for pediatric patients was successfully performed using clinical data. Size and maturation functions were applied according to established criteria, and single use of size function was applicable for over one year ages, while size and maturation functions were more effective for PK analysis of neonates and infants.
topic size function
maturation function
pharmacometrics
pediatrics
cyclosporin
phenobarbital
vancomycin
url https://www.mdpi.com/1999-4923/11/6/259
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