Developing pharmacokinetics – pharmacodynamics model of valproic acid syrup based on prediction of population pharmacokinetics parameter and seizure frequency in Indonesian pediatric epilepsy outpatients

Nugraha, I Komang Prawira Nata and Purnamayanti, Anita and Suwarba, I Gusti Ngurah Made and Parfati, Nani (2021) Developing pharmacokinetics – pharmacodynamics model of valproic acid syrup based on prediction of population pharmacokinetics parameter and seizure frequency in Indonesian pediatric epilepsy outpatients. Journal of Basic and Clinical Physiology and Pharmacology, 32 (4). pp. 305-311. ISSN 2191-0286

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Official URL / DOI: https://www.degruyter.com/document/doi/10.1515/jbc...

Abstract

Objectives: Valproic acid (VPA) is a broad spectrum antiepileptic drug with known efficacy profile in pediatric patients, despite of its narrow therapeutic index. There is lack of valproic acid’s pharmacokinetics profile in Indonesian pediatric subjects, partly due to limited pediatric blood volume taken for conducting therapeutic drug monitoring. This study aimed to determine the correlation between VPA pharmacokinetics parameters based on population data and seizure frequency in pediatric epilepsy outpatients. Methods: This observational study was conducted at Sanglah General Hospital during June – December 2019. The subject of this research were 38 pediatric epilepsy patients who adhered to valproic acid syrup monotherapy for at least 3 weeks. Five subject randomly selected for blood sample collection. Thus, valproic acid concentration level in the blood being analysed as a comparison to its concentration predicted from Yukawa’s steady state equation. Monolix2019R2® software was used to identify valproic acid population PK-PD parameters at steady state level. Results: Population pharmacokinetics-pharmacodynamics of valproic acid syrup at steady state level were ka_pop = 6.25/hour, Vd pop = 3.36 L, Cl pop = 3.17.e-11 mL/min., IC50 pop = 1.85.e-6, correlation of Vd_and Cl = 0.966. Kendall Tau Correlation of predicted valproic acid steady state concentration and frequency of seizure was -0.66. Mean prediction error between predicted steady state concentration of 5 subjects and their related blood levels was ≤ 25% and considered as within clinically acceptable limit. Conclusions: It needs further study to develop best matched PK-PD model of valproic acid syrup at steady state condition in pediatric epilepsy.

Item Type: Article
Uncontrolled Keywords: pediatric; population pharmacokinetics; prediction of concentration; seizure frequency; valproic acid
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy > Department of Pharmacy
Depositing User: Anita Purnamayanti Rahman 202021
Date Deposited: 01 Oct 2021 03:53
Last Modified: 01 Oct 2021 04:00
URI: http://repository.ubaya.ac.id/id/eprint/39817

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