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Open AccessArticle

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

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
College of Pharmacy, Seoul National University, Gwanak-ro 1, Gwanakgu, Seoul 08826, Korea
College of Pharmacy, Chungnam National University, Daehak-ro 99, Yuseonggu, Daejeon 34134, Korea
Ministry of Food and Drug Safety, Osongsangmyung 2-ro 187, Cheongju, Chungbuk 28159, Korea
JW Pharmaceutical Corp., Drug Discovery Center, Nambusunhwan-ro 2477, Seochogu, Seoul 06725, Korea
College of Pharmacy, Wonkwang University, Iksandae-ro 460, Iksan, Jeonbuk 54538, Korea
Department of Pharmacy, Kyunghee University Hospital at Gang-dong, Dongnam-ro 892, Kangdonggu, Seoul 05278, Korea
College of Pharmacy, Ewha Womans University, Ewhayeodae-gil 52, Seoul 03760, Korea
Department of Pharmacy, Yonsei University Health System, Yonsei-ro 50-1, Seodaemun-gu, Seoul 03722, Korea
Yangji Hospital, 1636 Nambusunhwan-ro, Gwanak-gu, Seoul 08779, Korea
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(6), 259;
Received: 10 April 2019 / Revised: 12 May 2019 / Accepted: 19 May 2019 / Published: 3 June 2019
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. View Full-Text
Keywords: size function; maturation function; pharmacometrics; pediatrics; cyclosporin; phenobarbital; vancomycin size function; maturation function; pharmacometrics; pediatrics; cyclosporin; phenobarbital; vancomycin
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Back, H.-M.; Lee, J.B.; Han, N.; Goo, S.; Jung, E.; Kim, J.; Song, B.; An, S.H.; Kim, J.T.; Rhie, S.J.; Ree, Y.S.; Chae, J.-W.; Kim, J.; Yun, H.-Y. Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients. Pharmaceutics 2019, 11, 259.

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