{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:02:27Z","timestamp":1790744547982,"version":"4.1.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with amyotrophic lateral sclerosis (ALS) frequently exhibit nonadherence characterized by delayed or missed doses while taking riluzole. This study aimed to provide a population pharmacokinetic (PPK) model informed individualized remedial regimens for patients who experience delayed or missed doses of riluzole.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A PPK model for riluzole was developed via a nonlinear mixed-effect modeling approach based on 3,024 concentration-time points from 72 subjects. The final model was validated by multiple methods. Six remedial regimens for missed doses were simulated for concentration-time profiles under different scenarios, and the optimal remedial regimen was selected based on the least time of concentration beyond the normal range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The PPK model of riluzole was best described with a two-compartment model with body weight as a covariate of peripheral distribution volume. The typical values of CL\/F, V\n                      <jats:sub>c<\/jats:sub>\n                      \/F, V\n                      <jats:sub>p<\/jats:sub>\n                      \/F and Q were 67\u00a0L\/h, 242\u00a0L, 376\u00a0L and 33.1\u00a0L\/h, respectively. The model was showed acceptable performance by goodness-of-fit, visual predictive check, bootstrap analysis and normalized distribution prediction errors. Model-based remedial regimens for different missed scenarios were proposed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A riluzole PPK model was developed and internally evaluated using multiple diagnostic approaches. Model-based remedial dosing strategies for different missed-dose scenarios were identified based on predefined PK criteria and Monte Carlo simulations. These exploratory strategies provide quantitative insights into riluzole exposure during nonadherent dosing conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1890355","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:53:52Z","timestamp":1790744032000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Handling missed dose of riluzole by population pharmacokinetic model informed remedial regimen"],"prefix":"10.3389","volume":"17","author":[{"given":"Changlong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Hangzhou Linping Hospital of Traditional Chinese Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Tang","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Pharmacy, Zhejiang University","place":["Hangzhou, China"]},{"name":"Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Yu","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Pharmacy, Zhejiang University","place":["Hangzhou, China"]},{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Pharmacy, Zhejiang University","place":["Hangzhou, China"]},{"name":"Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1080\/21678421.2020.1771734","article-title":"Real-world evidence of riluzole effectiveness in treating amyotrophic lateral sclerosis","volume":"21","author":"Andrews","year":"2020","journal-title":"Amyotroph. 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