Developing pharmacokinetics-pharmadynamics 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 and Parfati, Nani (2021) Developing pharmacokinetics-pharmadynamics model of Valproic Acid syrup based on prediction of population pharmacokinetics parameter and seizure frequency in Indonesian Pediatric Epilepsy Outpatients. Journal of Basic Clinical Physiology and Pharmacology, 32 (4). pp. 305-311.

	PDF Artikel_Final Manuscript-Developing PK-PD of Valproic Acid Syrup_Anita Purnamayanti.pdf Download (251kB)
	PDF Kelengkapan_Final Manuscript-Developing PK-PD of Valproic Acid Syrup_Anita Purnamayanti.pdf Download (28MB)

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 VPA’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 subjects of this research were 38 pediatric epilepsy patients who adhered to VPA syrup monotherapy for at least 3 weeks. Five subjects randomly selected for blood sample collection. Thus, VPA 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 VPA population pharmacokinetics–pharmacodynamics (PK–PD) parameters at steady state level. Results Population PK–PD of VPA syrup at steady state level were ka_pop = 6.25/h, Vd_pop = 3.36 L, Cl_pop = 3.17·e−11 mL/min, IC50_pop = 1.85·e−6, correlation of Vd_pop and Cl_pop = 0.966. Kendall Tau Correlation of predicted VPA steady state concentration and frequency of seizure was −0.66. Mean prediction error between predicted steady state concentration of five 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 VPA 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:	Postgraduate Programs > Master Program in Clinical Pharmacy
Depositing User:	Ester Sri W. 196039
Date Deposited:	15 Jan 2021 06:46
Last Modified:	23 Feb 2023 05:23
URI:	http://repository.ubaya.ac.id/id/eprint/38756

Actions (login required)

View Item