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Optimal Dosing Regimen of Phenytoin for Korean Epilepsy Patients: From Premature Babies to the Elderly

Authors
 Jinju Guk  ;  Sang-Guk Lee  ;  Dongwoo Chae  ;  Jeong-Ho Kim  ;  Kyungsoo Park 
Citation
 Journal of Pharmaceutical Sciences, Vol.108(8) : 2765-2773, 2019 
Journal Title
 Journal of Pharmaceutical Sciences 
ISSN
 0022-3549 
Issue Date
2019
Keywords
nonlinear mixed-effect model ; optimal dose regimen ; pharmacokinetic modeling ; phenytoin
Abstract
Phenytoin has been decreasingly used because of the high interindividual variability in drug concentration and the narrow therapeutic window. Despite such drawbacks, phenytoin is still essential as a second-line therapy for status epilepticus when patients are resistant to benzodiazepines. This study aimed to develop a population pharmacokinetic model of phenytoin and to propose the optimal dose regimen of phenytoin in Korean epilepsy patients. Concentrations collected from electronic medical records for 117 patients, with 1 or 2 measurements per patient, were analyzed using NONMEM 7.3.0. One-compartment model with first-order elimination where allometry scaling was considered best described the data, yielding the estimates of V and CL of 68.19 (L) and 0.63 (L/h), respectively, for patients with a body weight of 60 kg. Covariate analyses showed that, after birth, clearance increases with age, reaching adult level at 4 years, and after 20 years, it decreases with age. Simulation results showed that the dosing interval should be reduced to achieve optimal dosing in neonates and infants, and the optimal dose required increases with weight. This work demonstrates that a model-based approach can serve as a useful tool to individualize phenytoin therapy.
Full Text
https://www.sciencedirect.com/science/article/pii/S0022354919301716
DOI
10.1016/j.xphs.2019.03.022
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jeong Ho(김정호) ORCID logo https://orcid.org/0000-0003-2479-0548
Park, Kyungsoo(박경수) ORCID logo https://orcid.org/0000-0002-6972-1143
Lee, Sang-Guk(이상국) ORCID logo https://orcid.org/0000-0003-3862-3660
Chae, Dong Woo(채동우) ORCID logo https://orcid.org/0000-0002-7675-3821
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171330
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