{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T19:46:49Z","timestamp":1772480809426,"version":"3.50.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"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:p><jats:bold>Objectives:<\/jats:bold> Rituximab is frequently used off-label for the treatment of frequent-relapsing\/steroid-dependent nephrotic syndrome (FRNS\/SDNS). However, the optimal dosing schedules remain undetermined. The objective of this study was to establish a population pharmacokinetic-pharmacodynamic (PK-PD) model in pediatric patients with FRNS\/SDNS, and to investigate dosing regimens that provide adequate suppression of B lymphocytes.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A prospective, open-label, single-center study was conducted in Nephrology Department at Children\u2019s Hospital of Fudan University, and a two-compartment PK model of rituximab in pediatric FRNS\/SDNS has been developed previously by our group. CD19<jats:sup>+<\/jats:sup> lymphocyte count profiles were obtained from these patients. The presence of anti-rituximab antibodies was assessed prior to medication in children who had previously received rituximab or during follow-up at the last sampling point for PK analysis. PK-PD analyses were performed to describe the changes of CD19<jats:sup>+<\/jats:sup> lymphocytes, with rituximab assumed to increase their death rate. Monte Carlo simulation was conducted to evaluate different dosing regimens.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In total, 102 measurements of CD19<jats:sup>+<\/jats:sup> lymphocyte counts were available for PK-PD analysis. No detectable levels of anti-rituximab antibodies were observed during the PK follow-up period. A turnover model with saturable stimulatory action of rituximab on the removal of lymphocytes best characterized the relationship between rituximab concentration and CD19<jats:sup>+<\/jats:sup> lymphocyte counts, where the E<jats:sub>max<\/jats:sub> and EC<jats:sub>50<\/jats:sub> were estimated to be 99.6*10<jats:sup>6<\/jats:sup>\/L and 5.87\u00a0\u03bcg\/mL, respectively. Simulations indicated that a single infusion of 750\u00a0mg\/m<jats:sup>2<\/jats:sup> and 2 infusions of 375\u00a0mg\/m<jats:sup>2<\/jats:sup> both yielded a 10-week suppression of CD19<jats:sup>+<\/jats:sup> lymphocytes.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study represents a first attempt to quantitatively describe the PK-PD relationship of rituximab in pediatric patients with FRNS\/SDNS, and provide a potential pathway for future precision dosing strategy for rituximab therapy. Further clinical studies are warranted to evaluate the efficacy and safety of different dosing schemes.<\/jats:p>","DOI":"10.3389\/fphar.2023.1319744","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T04:15:20Z","timestamp":1704773720000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Using real-world data to inform dosing strategies of rituximab for pediatric patients with frequent-relapsing or steroid-dependent nephrotic syndrome: a prospective pharmacokinetic-pharmacodynamic study"],"prefix":"10.3389","volume":"14","author":[{"given":"Yewei","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiping","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2481","DOI":"10.2217\/fon.14.146","article-title":"Rituximab: modes of action, remaining dispute and future perspective","volume":"10","author":"Abulayha","year":"2014","journal-title":"Future Oncol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1007\/s00467-014-2794-7","article-title":"Development of antirituximab antibodies in children with nephrotic syndrome","volume":"29","author":"Ahn","year":"2014","journal-title":"Pediatr. 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