{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:55:01Z","timestamp":1790391301321,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pimavanserin is a selective serotonin\u2010modulating agent with inverse agonist\/antagonist activity at the 5\u2010hydroxytryptamine<jats:sub>2A<\/jats:sub> (5\u2010HT<jats:sub>2A<\/jats:sub>) receptor. The safety and efficacy of pimavanserin 34\u00a0mg once daily were studied in adults with hallucinations and delusions associated with Parkinson's disease psychosis and other neuropsychiatric conditions. This analysis used model\u2010based simulations of pimavanserin steady\u2010state exposures to identify a dose that generated pediatric exposures comparable with adult exposures achieved with 34\u00a0mg pimavanserin. A population pharmacokinetics model was developed using pooled plasma drug concentration (ie, actual) data from 13 clinical studies, including a phase\u00a01 study of adolescent pediatric patients (aged 13\u201017\u00a0years) with various psychiatric conditions. Stochastic simulations were performed to predict exposures in a virtual (ie, simulated) group of pediatric patients (aged 5\u201017\u00a0years). Steady\u2010state measures of the area under the plasma concentration\u2013time curve (AUC) and maximum drug concentration (C<jats:sub>max<\/jats:sub>) were simulated for relevant age and weight stratifications and compared with simulated exposures in adults (aged 18\u201049\u00a0years). The simulated mean AUC ranged from 47.41 to 54.73\u00a0ng d\/mL and the mean C<jats:sub>max<\/jats:sub> ranged from 41.13 to 50.07\u00a0ng\/mL in adults receiving pimavanserin 34\u00a0mg. The simulated mean (SD) C<jats:sub>max<\/jats:sub> of 56.54\u00a0(24.58)\u00a0ng\/mL with pimavanserin 34\u00a0mg in patients aged 10\u201017\u00a0years was similar to that in adults. Pimavanserin 20\u00a0mg yielded a mean (SD) C<jats:sub>max<\/jats:sub> of 45.30\u00a0(21.31)\u00a0ng\/mL in patients aged 5\u20109\u00a0years and 49.18\u00a0(22.91)\u00a0ng\/mL in the pediatric patient weight group of 14\u201025\u00a0kg, which are values close to the C<jats:sub>max<\/jats:sub> in adults treated with 34\u00a0mg. Pimavanserin 20 and 34\u00a0mg in pediatric patients aged 5\u20109 and 10\u201017\u00a0years, respectively, yielded exposures similar to daily pimavanserin 34\u00a0mg in adults aged 18\u201049\u00a0years.<\/jats:p>","DOI":"10.1002\/jcph.2315","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T19:28:50Z","timestamp":1689881330000},"page":"1408-1416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Population Pharmacokinetic Modeling and Stochastic Simulations to Support Pediatric Dose Selection of Pimavanserin"],"prefix":"10.1002","volume":"63","author":[{"given":"Mona","family":"Darwish","sequence":"first","affiliation":[{"name":"Acadia Pharmaceuticals Inc. Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragana","family":"Bugarski\u2010Kirola","sequence":"additional","affiliation":[{"name":"Acadia Pharmaceuticals GmbH Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jaworowicz","sequence":"additional","affiliation":[{"name":"Cognigen Corporation a Simulations\u2010Plus company Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Owen","sequence":"additional","affiliation":[{"name":"Cognigen Corporation a Simulations\u2010Plus company Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Al Qaraghuli","sequence":"additional","affiliation":[{"name":"Cognigen Corporation a Simulations\u2010Plus company Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alida","family":"Barry","sequence":"additional","affiliation":[{"name":"Acadia Pharmaceuticals Inc. 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Accessed November 26 2019.https:\/\/www.cdc.gov\/growthcharts\/zscore.htm"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T12:41:25Z","timestamp":1699533685000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.2315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,17]]},"references-count":17,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/jcph.2315"],"URL":"https:\/\/doi.org\/10.1002\/jcph.2315","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,17]]},"assertion":[{"value":"2022-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}