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This study aimed to establish a pharmacokinetic (PK)\u2013pharmacodynamic (PD) model to explore the impact of chemotherapy and tripegfilgrastim on absolute neutrophil counts (ANCs) and to further propose a fixed\u2010dose regimen in pediatric patients. Because neutrophils affect the clearance of tripegfilgrastim, the semimechanistic PK\u2010PD model was developed simultaneously by using data from 40 healthy adults and 27 pediatric patients with solid tumors. Tripegfilgrastim PK and ANC dynamics were described with a pharmacodynamics\u2010mediated drug disposition model assuming quasi\u2010equilibrium with five transit compartments mimicking neutrophil granulopoiesis. The effect of chemotherapy on neutrophils was included by stimulating the elimination of the G\u2010CSF receptor at the mitotic cells. Healthy adult and pediatric patients showed significantly different value for dissociation constant of the tripegfilgrastim\u2010G\u2010CSF receptor complex (K<jats:sub>d<\/jats:sub>) and apparent volume of distribution (V<jats:sub>d<\/jats:sub>\/F). Patients treated with chemotherapy had a higher V<jats:sub>d<\/jats:sub>\/F and 62% lower K<jats:sub>d<\/jats:sub> than healthy adults. As the age increased, the absorption rate of tripegfilgrastim was decreased. Body weight affected the G\u2010CSF receptor\u2010mediated internalization of tripegfilgrastim, and the baseline ANC value impacted the production rate of G\u2010CSF receptors. Simulations from the developed model suggested that 1.5, 2.5, 4, and 6\u2009mg single subcutaneous tripegfilgrastim doses for the respective weight groups of 10\u201320, 21\u201330, 31\u201344, and more than 45\u2009kg significantly reduced the duration of Grade 4 neutropenia similar to tripegfilgrastim weight\u2010based treatment with 100\u2009\u03bcg\/kg.<\/jats:p>","DOI":"10.1002\/psp4.13012","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T05:17:41Z","timestamp":1691644661000},"page":"1319-1334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Semimechanistic pharmacokinetic\u2013pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-4489","authenticated-orcid":false,"given":"Soyoung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of 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