{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:42:13Z","timestamp":1792302133418,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T00:00:00Z","timestamp":1519776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Population pharmacokinetics is an essential tool that helps guide individualized dosing regimens. The aims of this systematic review are to provide knowledge concerning population pharmacokinetics of valproic acid (VPA) and to identify factors influencing VPA pharmacokinetic variability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed and Embase databases were systematically searched from inception to June, 2017. Relevant articles from reference lists were also included. All population pharmacokinetic studies of VPA conducted in humans and that employed a nonlinear mixed effect modelling approach were included in this review.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010six studies were included in this review. Most studies characterized VPA pharmacokinetics as a one\u2010compartment model. Three studies reported a two\u2010compartment model. Body weight, dose and age were significant predictors for VPA volume of distribution (\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>d<\/jats:sub>\n                      ). The estimated\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>d<\/jats:sub>\n                      for one\u2010compartment models ranged from 8.4 to 23.3\u00a0l. For two\u2010compartment models, peripheral volumes of distribution ranged from 4.08 to 42.1\u00a0l. Frequently reported significant predictors for VPA clearance (CL\n                      <jats:sub>VPA<\/jats:sub>\n                      ) included body weight, VPA dose, concomitant medications, gender and age. The estimated CL\n                      <jats:sub>VPA<\/jats:sub>\n                      ranged from 0.206 to 1.154\u00a0l\u00a0h\n                      <jats:sup>\u22121<\/jats:sup>\n                      and the inter\u2010individual variability ranged from 13.40 to 35.90%. Two studies reported population pharmacokinetics\/pharmacodynamics of VPA in patients with epilepsy. Seventeen studies evaluated the performance of their final models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Significant predictors influencing VPA pharmacokinetics as well as model methodologies are highlighted in this review. For clinical application, CL\n                      <jats:sub>VPA<\/jats:sub>\n                      could be predicted using body weight, VPA dose, concomitant medications, gender or age. For future research, there is a knowledge gap regarding population pharmacokinetics\/pharmacodynamics of VPA in a population other than epileptic patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.13510","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T10:26:38Z","timestamp":1515752798000},"page":"816-834","source":"Crossref","is-referenced-by-count":100,"title":["A systematic review of population pharmacokinetics of valproic acid"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5142-8769","authenticated-orcid":false,"given":"Janthima","family":"Methaneethorn","sequence":"first","affiliation":[{"name":"Pharmacokinetic Research Unit, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences Naresuan University  Phitsanulok Thailand"},{"name":"Center of Excellence for Environmental Health and Toxicology Naresuan University  Phitsanulok 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