{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:50:03Z","timestamp":1788202203841,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sirolimus is confirmed to be effective in the treatment of tuberous sclerosis complex (TSC) and related disorders. The study aims to establish a population pharmacokinetic model of oral sirolimus for children with TSC and provide an evidence\u2010based approach for individualization of sirolimus dosing in the pediatric population. A total of 64 children were recruited in this multicenter, retrospective pharmacokinetic study. Whole\u2010blood concentrations of sirolimus, demographic, and clinical information were collected and analyzed using a nonlinear mixed\u2010effects population modeling method. The final model was internally and externally validated. Then Monte Carlo simulations were performed to evaluate and optimize the dosing regimens. In addition, the efficacy and safety of sirolimus therapy was assessed retrospectively in patients with epilepsy or cardiac rhabdomyomas associated with TSC. Finally, the sirolimus pharmacokinetic profile was described by a 1\u2010compartment model with first\u2010order absorption and elimination along with body weight and total daily dose as significant covariates. The typical population parameter estimates of apparent volume of distribution and apparent clearance were 69.48 L and 2.79 L\/h, respectively. Simulations demonstrated that dosage regimens stratified by body surface area may be more appropriate for children with TSC. These findings could be used to inform individualized dosing strategies of sirolimus for pediatric patients with TSC.<\/jats:p>","DOI":"10.1002\/jcph.2033","type":"journal-article","created":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T11:49:32Z","timestamp":1643543372000},"page":"948-959","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Population Pharmacokinetic Analysis and Dosing Optimization of Sirolimus in Children With Tuberous Sclerosis Complex"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8526-1634","authenticated-orcid":false,"given":"SiChan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan People's Republic of China"},{"name":"Clinical Medical Research Center for 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