{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:35:15Z","timestamp":1792841715085,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Infliximab is an anti-TNF-\u03b1 monoclonal antibody approved in chronic inflammatory bowel diseases (IBD). This study aimed at providing an in-depth description of infliximab target-mediated pharmacokinetics in 133 IBD patients treated with 5 mg\/kg infliximab at weeks 0, 2, 14, and 22. A two-compartment model with double target-mediated drug disposition (TMDD) in both central and peripheral compartments was developed, using a rich database of 26 ankylosing spondylitis patients as a reference for linear elimination kinetics. Population approach and quasi-steady-state (QSS) approximation were used. Concentration-time data were satisfactorily described using the double-TMDD model. Target-mediated parameters of central and peripheral compartments were respectively baseline TNF concentrations (RC0 = 3.3 nM and RP0 = 0.46 nM), steady-stated dissociation rates (KCSS = 15.4 nM and KPSS = 0.49 nM), and first-order elimination rates of complexes (kCint = 0.17 day\u22121 and kPint = 0.0079 day\u22121). This model showed slower turnover of targets and infliximab-TNF complex elimination rate in peripheral compartment than in central compartment. This study allowed a better understanding of the multi-scale target-mediated pharmacokinetics of infliximab. This model could be useful to improve model-based therapeutic drug monitoring of infliximab in IBD patients.<\/jats:p>","DOI":"10.3390\/pharmaceutics13111821","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:24:22Z","timestamp":1635805462000},"page":"1821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Infliximab Efficacy May Be Linked to Full TNF-\u03b1 Blockade in Peripheral Compartment\u2014A Double Central-Peripheral Target-Mediated Drug Disposition (TMDD) Model"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4020-4545","authenticated-orcid":false,"given":"David","family":"Ternant","sequence":"first","affiliation":[{"name":"EA 4245 \u201cTransplantation, Immunology, Inflammation\u201d, Universit\u00e9 de Tours, 37044 Tours, France"},{"name":"Department of Clinical Pharmacology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Le Tilly","sequence":"additional","affiliation":[{"name":"EA 4245 \u201cTransplantation, Immunology, Inflammation\u201d, Universit\u00e9 de Tours, 37044 Tours, France"},{"name":"Department of Clinical Pharmacology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Picon","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Driffa","family":"Moussata","sequence":"additional","affiliation":[{"name":"EA 4245 \u201cTransplantation, Immunology, Inflammation\u201d, Universit\u00e9 de Tours, 37044 Tours, France"},{"name":"Department of Gastroenterology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Passot","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biopathologie, Institut de Canc\u00e9rologie de l\u2019Ouest, 49055 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Bejan-Angoulvant","sequence":"additional","affiliation":[{"name":"EA 4245 \u201cTransplantation, Immunology, Inflammation\u201d, Universit\u00e9 de Tours, 37044 Tours, France"},{"name":"Department of Clinical Pharmacology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5102-5908","authenticated-orcid":false,"given":"C\u00e9line","family":"Desvignes","sequence":"additional","affiliation":[{"name":"EA 4245 \u201cTransplantation, Immunology, Inflammation\u201d, Universit\u00e9 de Tours, 37044 Tours, France"},{"name":"Department of Clinical Pharmacology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4089-7513","authenticated-orcid":false,"given":"Denis","family":"Mulleman","sequence":"additional","affiliation":[{"name":"EA 7501 \u201cGroupe Innovation et Ciblage Cellulaire\u201d, Universit\u00e9 de Tours, 37044 Tour, France"},{"name":"Department of Rheumatology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Goupille","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Paintaud","sequence":"additional","affiliation":[{"name":"EA 4245 \u201cTransplantation, Immunology, Inflammation\u201d, Universit\u00e9 de Tours, 37044 Tours, France"},{"name":"Department of Clinical Pharmacology, CHRU de Tours, 37044 Tour, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/FTD.0000000000000410","article-title":"Rationale for Therapeutic Drug Monitoring of Biopharmaceuticals in Inflammatory Diseases","volume":"39","author":"Paintaud","year":"2017","journal-title":"Ther. 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