{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:40:05Z","timestamp":1790368805501,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>(1) Background: The aim of this study was to explore the valproic acid (VPA) pharmacokinetic characteristics in a large population of pediatric and adult Caucasian patients and to establish a robust population pharmacokinetic (PopPK) model. (2) Methods: A total of 2527 serum VPA samples collected from 1204 patients included in a therapeutic drug monitoring program were retrospectively analyzed. Patients were randomly assigned to either a model development group or an external evaluation group. PopPK analysis was performed on 1751 samples from 776 patients with NONMEM using a nonlinear mixed-effect modelling approach. The influence of demographic, anthropometric, treatment and comedication variables on the apparent clearance (CL\/F) of VPA was studied. The bootstrap method was used to evaluate the final model internally. External evaluation was carried out using 776 VPA serum samples from 368 patients. (3) Results: A one-compartment model with first-order absorption and elimination successfully described the data. The final model included total body weight, age and comedication with phenytoin, phenobarbital and carbamazepine with a significant impact on VPA elimination. Internal and external evaluations demonstrated the good predictability of the model. (4) Conclusions: A PopPK model of VPA in Caucasian patients was successfully established, which will be helpful for model-informed precision dosing approaches in clinical patient care.<\/jats:p>","DOI":"10.3390\/pharmaceutics14040811","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T21:08:22Z","timestamp":1649365702000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4677-4784","authenticated-orcid":false,"given":"Paulo","family":"Teixeira-da-Silva","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Department, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Pharmacy Service, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1232-1763","authenticated-orcid":false,"given":"Jon\u00e1s Samuel","family":"P\u00e9rez-Blanco","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Pharmacy Service, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8236-6537","authenticated-orcid":false,"given":"Dolores","family":"Santos-Buelga","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Pharmacy Service, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6468-8842","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"Otero","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Pharmacy Service, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2760-7083","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Pharmacy Service, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00228-018-2444-2","article-title":"A Population Pharmacokinetic Model Taking into Account Protein Binding for the Sustained-Release Granule Formulation of Valproic Acid in Children with Epilepsy","volume":"74","author":"Rodrigues","year":"2018","journal-title":"Eur. 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