{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:31:32Z","timestamp":1791178292413,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T00:00:00Z","timestamp":1421712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2015,2]]},"abstract":"\n Aims<\/jats:title>\n \n This study aimed at describing adalimumab pharmacokinetics (\n PK<\/jats:styled-content>\n ) and the concentration\u2013effect relationship of adalimumab using pharmacokinetic\u2013pharmacodynamic (\n PK\u2013PD<\/jats:styled-content>\n ) modelling in patients with rheumatoid arthritis (\n RA<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Adalimumab\n PK<\/jats:styled-content>\n and\n PK\u2013PD<\/jats:styled-content>\n data were obtained from a multicentric observational study. Adalimumab (40\u2009mg) was administered subcutaneously every other week, and its pharmacokinetics was described using a one\u2010compartment model. The relationship between adalimumab concentration and\n C<\/jats:styled-content>\n \u2010reactive protein (\n CRP<\/jats:styled-content>\n ) concentration was described using an indirect response model with inhibition of\n CRP<\/jats:styled-content>\n input, whereas the relationship between adalimumab concentration and disease activity score in 28 joints (\n DAS28<\/jats:styled-content>\n ) was described using a direct inhibition model. Dose regimens that included a loading dose of adalimumab were simulated.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Thirty patients treated for\n RA<\/jats:styled-content>\n were analysed. The following pharmacokinetic and\n PK\u2013PD<\/jats:styled-content>\n parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (\n \n V<\/jats:styled-content>\n <\/jats:italic>\n d<\/jats:sub>\n \/\n \n F<\/jats:styled-content>\n <\/jats:italic>\n )\u2009=\u200910.8\u2009l (92%); apparent clearance (\n CL<\/jats:styled-content>\n \/\n \n F<\/jats:styled-content>\n <\/jats:italic>\n )\u2009=\u20090.32\u2009l\u2009day\n \u22121<\/jats:sup>\n (17%); first\u2010order absorption rate (\n k<\/jats:italic>\n a<\/jats:sub>\n )\u2009=\u20090.28 day\n \u22121<\/jats:sup>\n ;\n CRP<\/jats:styled-content>\n input (\n k<\/jats:italic>\n in<\/jats:sub>\n )\u2009=\u200922.0\u2009mg\u2009l\n \u22121<\/jats:sup>\n \u2009day\n \u22121<\/jats:sup>\n (65%); adalimumab concentration leading to a 50% decrease in\n k<\/jats:italic>\n in<\/jats:sub>\n (\n C<\/jats:italic>\n 50<\/jats:sub>\n )\u2009=\u20093.6\u2009mg\u2009l\n \u22121<\/jats:sup>\n (88%); baseline DAS28 (DAS\n 0<\/jats:sub>\n )\u2009=\u20095.5\u2009mg\u2009l\n \u22121<\/jats:sup>\n (11%); and adalimumab concentration leading to 50% decrease of DAS\n 0<\/jats:sub>\n (IC\n 50<\/jats:sub>\n )\u2009=\u200911.0\u2009mg\u2009l\n \u22121<\/jats:sup>\n (71%). Simulations showed that a 160\u2009mg loading dose should reduce the time to reach efficacy in terms of both\n CRP<\/jats:styled-content>\n and DAS28 after the first injection.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This is the first study to describe adalimumab pharmacokinetics and the concentration\u2013effect relationship in\n RA<\/jats:styled-content>\n . A 160\u2009mg loading dose may lead to an increased benefit from treatment in\n RA<\/jats:styled-content>\n patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bcp.12509","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T00:46:21Z","timestamp":1410828381000},"page":"286-297","source":"Crossref","is-referenced-by-count":92,"title":["Pharmacokinetics and concentration\u2013effect relationship of adalimumab in rheumatoid arthritis"],"prefix":"10.1111","volume":"79","author":[{"given":"David","family":"Ternant","sequence":"first","affiliation":[{"name":"CNRS, UMR 7292 \u2018Genetics, Immunotherapy, Chemistry and Cancer\u2019 Universit\u00e9 Fran\u00e7ois Rabelais de Tours Tours France"},{"name":"Laboratoire de pharmacologie\u2010toxicologie CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Ducourau","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7292 \u2018Genetics, Immunotherapy, Chemistry and Cancer\u2019 Universit\u00e9 Fran\u00e7ois Rabelais de Tours Tours France"},{"name":"Service de Rhumatologie CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pi\u00e9ra","family":"Fuzibet","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7292 \u2018Genetics, Immunotherapy, Chemistry and Cancer\u2019 Universit\u00e9 Fran\u00e7ois Rabelais de Tours Tours France"},{"name":"Service de Rhumatologie CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Vignault","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7292 \u2018Genetics, Immunotherapy, Chemistry and Cancer\u2019 Universit\u00e9 Fran\u00e7ois Rabelais de Tours Tours France"},{"name":"Laboratoire de pharmacologie\u2010toxicologie CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Watier","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7292 \u2018Genetics, Immunotherapy, Chemistry and Cancer\u2019 Universit\u00e9 Fran\u00e7ois Rabelais de Tours Tours France"},{"name":"Laboratoire d'Immunologie CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lequerr\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rouen INSERM U905 & CIC\/CRB0204 Rouen France"},{"name":"CHRU de Rouen Service de Rhumatologie Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Le Lo\u00ebt","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rouen INSERM U905 & CIC\/CRB0204 Rouen France"},{"name":"CHRU de Rouen Service de Rhumatologie Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Vittecoq","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rouen INSERM U905 & CIC\/CRB0204 Rouen France"},{"name":"CHRU de Rouen Service de Rhumatologie Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Goupille","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7292 \u2018Genetics, Immunotherapy, Chemistry and Cancer\u2019 Universit\u00e9 Fran\u00e7ois Rabelais de Tours Tours France"},{"name":"Service de Rhumatologie CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Mulleman","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7292 \u2018Genetics, Immunotherapy, Chemistry and Cancer\u2019 Universit\u00e9 Fran\u00e7ois Rabelais de Tours Tours France"},{"name":"Service de Rhumatologie CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Paintaud","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7292 \u2018Genetics, Immunotherapy, Chemistry and Cancer\u2019 Universit\u00e9 Fran\u00e7ois Rabelais de Tours Tours France"},{"name":"Laboratoire de pharmacologie\u2010toxicologie CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,20]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"FDA.Adalimumab indications and usage. 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