{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:05:06Z","timestamp":1760598306917,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>In this study, a physiologically based pharmacokinetic (PBPK) modeling framework was employed to explore infliximab exposure following intravenous (5 mg\/kg) and subcutaneous administration (encompassing the approved 120 mg flat-fixed dose as a switching option) in virtual adult and pediatric patients with inflammatory bowel disease (IBD). The PBPK model and corresponding simulations were conducted using the PK-Sim\u00ae software platform. The PBPK simulation indicated that a 120 mg subcutaneous flat-fixed dose might not be optimal for heavier adults with IBD, suggesting the need for infliximab dose escalation. For an older virtual pediatric patient (14 years old), subcutaneous administration of a 120 mg flat-fixed dose appears to be a feasible IBD treatment option. In the final exploration scenario, the model was extended to predict hypothetical subcutaneous infliximab doses in a virtual pediatric population (6\u201318 years old), stratified into three weight bands (20\u201330 kg, 30\u201345 kg, and 45\u201370 kg), that would yield post-switch trough concentrations of infliximab comparable to those seen in adults with the 120 mg flat-fixed subcutaneous dose. The PBPK-model-informed dose suggestions were 40 mg for the 20\u201330 kg band, 80 mg for the 30\u201345 kg band, and 120 mg for the 45\u201370 kg band. As demonstrated in this paper, the PBPK modeling framework can serve as a versatile tool in clinical pharmacology to investigate various clinical scenarios, such as exploring alternative dosing regimens and routes of administration, ultimately advancing IBD treatment across diverse (sub)populations of clinical interest.<\/jats:p>","DOI":"10.3390\/biomedicines12091974","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T06:51:17Z","timestamp":1725259877000},"page":"1974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Infliximab in Inflammatory Bowel Disease: Leveraging Physiologically Based Pharmacokinetic Modeling in the Clinical Context"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2127-8605","authenticated-orcid":false,"given":"Zvonimir","family":"Petric","sequence":"first","affiliation":[{"name":"Department of Pharmacological Sciences, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, 1649-004 Lisbon, Portugal"}]},{"given":"Jo\u00e3o","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Biopharmaceutical and Molecular Biotechnology Unit, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, 1649-004 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6554-4840","authenticated-orcid":false,"given":"Paulo","family":"Paix\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, 1649-004 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Petric, Z., Goncalves, J., and Paixao, P. 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