{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:16:01Z","timestamp":1747196161907,"version":"3.40.5"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Method<\/jats:title>\n<jats:p>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\u00ae 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>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 (V<jats:sub>d<\/jats:sub>) 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 V<jats:sub>d<\/jats:sub>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0272622","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T17:31:48Z","timestamp":1661362308000},"page":"e0272622","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparative pharmacokinetics of valproic acid among Pakistani and South Korean patients: A population pharmacokinetic study"],"prefix":"10.1371","volume":"17","author":[{"given":"Muhammad","family":"Usman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qurrat-ul-Ain","family":"Shaukat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Imran","family":"Khokhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabiea","family":"Bilal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rizwan Rasul","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hafiz Asad","family":"Saeed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsin","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8139-9890","authenticated-orcid":true,"given":"Humaira Majeed","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"pone.0272622.ref001","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1527-3458.2003.tb00249.x","article-title":"Valproate: past, present, and future","volume":"9","author":"CU Johannessen","year":"2003","journal-title":"CNS drug reviews"},{"volume-title":"Basic clinical pharmacokinetics5th","year":"2010","author":"ME Winter","key":"pone.0272622.ref002"},{"key":"pone.0272622.ref003","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/1177391X0800200001","article-title":"Modifications of antiepileptic drugs for improved tolerability and efficacy","volume":"2","author":"CJ Landmark","year":"2008","journal-title":"Perspect Medicin Chem"},{"key":"pone.0272622.ref004","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1210\/en.2004-0877","article-title":"Valproic acid inhibits leptin secretion and reduces leptin messenger ribonucleic acid levels in adipocytes","volume":"145","author":"DC Lagace","year":"2004","journal-title":"Endocrinol"},{"key":"pone.0272622.ref005","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1111\/bcp.13510","article-title":"A systematic review of population pharmacokinetics of valproic acid","volume":"84","author":"J. 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