Pharmacokinetic modeling of valproate from clinical data in Serbian epileptic patients

Methods and Findings in Experimental and Clinical Pharmacology
S Jankovic, Jasmina R Milovanovic

Abstract

The aim of this study was to define a population pharmacokinetic model that could estimate the clearance of valproate (VPA) in a Serbian epileptic population. For the analysis, 97 steady-state concentrations of VPA were used, collected from 93 patients with epilepsy during routine clinical care in our hospital. To build a final model, we selected the ADVAN1 program subroutine from the NONMEM library for estimating the drug clearance (CL) and determining the influence of different covariates. This is a one-compartment model with first-order elimination and without absorption. Estimation of the predictive performances of the final model was performed on a validation set consisting of 20 epileptic patients. Typical mean value of CL of VPA estimated by the base model in our population was 0.368 l h(-1). The results of the final model show that the CL of VPA increased linearly with total body weight (TBW) and patients' age, while carbamazepine (CBZ) comedication did not affect it significantly. Interindividual variability (coefficient of variation) for CL was 27.2%. Residual error, including intraindividual variability, was 29.68%. The results of the validation process and the analysis of prediction errors suggest a good predictive ...Continue Reading

Citations

Dec 29, 2010·Medicinski pregled·Mihajlo B JakovljevićSnezana Janković
Jun 22, 2019·International Journal of Clinical Pharmacy·Saeed AlqahtaniAbdullah Alsultan
Sep 29, 2020·Journal of Clinical Pharmacy and Therapeutics·Janthima Methaneethorn, Nattawut Leelakanok
Jan 13, 2018·British Journal of Clinical Pharmacology·Janthima Methaneethorn

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