Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy

Abstract This study aimed to develop a pharmacokinetic (PK) model of oxcarbazepine (OXC) and analyse the relationship between monohydroxylated derivative (MHD), an active metabolite of OXC, and the adverse events of OXC. We obtained 711 OXC samples from 618 patients with epilepsy who were enrolled i...

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Autores principales:	Yoonhyuk Jang, Seonghae Yoon, Tae-Joon Kim, SeungHwan Lee, Kyung-Sang Yu, In-Jin Jang, Kon Chu, Sang Kun Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c0150e2099e43f5a9056c9e990cf932
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spelling	oai:doaj.org-article:6c0150e2099e43f5a9056c9e990cf9322021-12-02T11:39:20ZPopulation pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy10.1038/s41598-021-85920-02045-2322https://doaj.org/article/6c0150e2099e43f5a9056c9e990cf9322021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85920-0https://doaj.org/toc/2045-2322Abstract This study aimed to develop a pharmacokinetic (PK) model of oxcarbazepine (OXC) and analyse the relationship between monohydroxylated derivative (MHD), an active metabolite of OXC, and the adverse events of OXC. We obtained 711 OXC samples from 618 patients with epilepsy who were enrolled in the Epilepsy Registry Cohort of Seoul National University Hospital from February 2011 to January 2014. The plasma PK model was developed using a nonlinear mixed-effect modelling method with NONMEM (ver 7.3). A one-compartment model with a first-order absorption model and proportional residual error adequately described the MHD concentration–time profiles. The only covariate incorporated for CL/F and V/F was body weight. Of the 447 patients analysed, 28 (6.26%) had dose-related adverse events (DRAEs), which were dizziness, somnolence, headache, and diplopia. For DRAE occurrence, the cut-off values of the MHD trough and AUC were 12.27 mg/L (specificity 0.570, sensitivity 0.643) and 698.5 mg h/L (specificity, sensitivity 0.571), respectively. Multivariate analysis showed the sole dizziness symptom was significantly associated with both the MHD trough and the AUC (p = 0.013, p = 0.038, respectively). We newly developed a population PK model using sparse sampling data from patients with epilepsy, and the model better reflects the actual clinical situation.Yoonhyuk JangSeonghae YoonTae-Joon KimSeungHwan LeeKyung-Sang YuIn-Jin JangKon ChuSang Kun LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoonhyuk Jang Seonghae Yoon Tae-Joon Kim SeungHwan Lee Kyung-Sang Yu In-Jin Jang Kon Chu Sang Kun Lee Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy
description	Abstract This study aimed to develop a pharmacokinetic (PK) model of oxcarbazepine (OXC) and analyse the relationship between monohydroxylated derivative (MHD), an active metabolite of OXC, and the adverse events of OXC. We obtained 711 OXC samples from 618 patients with epilepsy who were enrolled in the Epilepsy Registry Cohort of Seoul National University Hospital from February 2011 to January 2014. The plasma PK model was developed using a nonlinear mixed-effect modelling method with NONMEM (ver 7.3). A one-compartment model with a first-order absorption model and proportional residual error adequately described the MHD concentration–time profiles. The only covariate incorporated for CL/F and V/F was body weight. Of the 447 patients analysed, 28 (6.26%) had dose-related adverse events (DRAEs), which were dizziness, somnolence, headache, and diplopia. For DRAE occurrence, the cut-off values of the MHD trough and AUC were 12.27 mg/L (specificity 0.570, sensitivity 0.643) and 698.5 mg h/L (specificity, sensitivity 0.571), respectively. Multivariate analysis showed the sole dizziness symptom was significantly associated with both the MHD trough and the AUC (p = 0.013, p = 0.038, respectively). We newly developed a population PK model using sparse sampling data from patients with epilepsy, and the model better reflects the actual clinical situation.
format	article
author	Yoonhyuk Jang Seonghae Yoon Tae-Joon Kim SeungHwan Lee Kyung-Sang Yu In-Jin Jang Kon Chu Sang Kun Lee
author_facet	Yoonhyuk Jang Seonghae Yoon Tae-Joon Kim SeungHwan Lee Kyung-Sang Yu In-Jin Jang Kon Chu Sang Kun Lee
author_sort	Yoonhyuk Jang
title	Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy
title_short	Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy
title_full	Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy
title_fullStr	Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy
title_full_unstemmed	Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy
title_sort	population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6c0150e2099e43f5a9056c9e990cf932
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Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy

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