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. 2022 Aug 24;17(8):e0272622.
doi: 10.1371/journal.pone.0272622. eCollection 2022.

Comparative pharmacokinetics of valproic acid among Pakistani and South Korean patients: A population pharmacokinetic study

Muhammad Usman  1 , Qurrat-Ul-Ain Shaukat  2 , Muhammad Imran Khokhar  3   4 , Rabiea Bilal  5 , Rizwan Rasul Khan  6 , Hafiz Asad Saeed  7 , Mohsin Ali  8 , Humaira Majeed Khan  2
Affiliations

Comparative pharmacokinetics of valproic acid among Pakistani and South Korean patients: A population pharmacokinetic study

Muhammad Usman et al. PLoS One. .

Abstract

Purpose: The pharmacokinetics of valproic acid have been evaluated in a variety of populations however, the comparison in two different populations was yet to be reported. This study is aimed to compare the pharmacokinetics of valproic acid in Pakistani and South Korean patients.

Method: The therapeutic drug monitoring (TDM) data of valproic acid from 92 Pakistani patients with 218 samples was combined with the data of 99 South Korean patients with 335 samples in order to form a pooled dataset of 191 patients with 553 samples. Population pharmacokinetic model was developed on NONMEM® software by using first order conditional estimation method for estimation of pharmacokinetic parameters. The influence of different covariates including ethnicity was evaluated the stepwise covariate modelling. The final model was evaluated for predictive performance and robustness by using goodness of fit plots and bootstrap analysis respectively.

Results: The data was better described by one compartment model with first order elimination. The value for clearance (CL) of valproic in pooled data was 0.931 L/h with 43.4% interindividual variability (IIV) while volume of distribution (Vd) was 16.6 L with 22.3% IIV. In covariate analysis, ethnicity and body weight were significant covariates for CL while body weight was also significant for Vd.

Conclusion: A significant difference in CL of valproic acid among Pakistani and South Korean patients was observed. The model can be used for the dose tailoring of valproic acid based on ethnicity and body weight of Pakistani and South Korean patients.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
Box-plots showing CL (a) and Vd (b) of valproic acid among Pakistani and South Korean patients.
Fig 2
Fig 2
Goodness-of-fit plots of final model showing observed concentrations vs. individual predictions (a), observed concentrations vs. population predictions (b), CWRES vs. population predictions (c) and CWRES vs. time after dose (d).
See this image and copyright information in PMC

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