{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:52:15Z","timestamp":1790218335636,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,25]],"date-time":"2018-06-25T00:00:00Z","timestamp":1529884800000},"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":[[2018,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The purpose of this study was to characterize pharmacokinetics (PK) of PF\u201004236921, a novel anti\u2010interleukin\u20106 monoclonal antibody, and its pharmacokinetic\/pharmacodynamic (PK\/PD) relationship on serum C\u2010reactive protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Crohn's disease (CD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from two phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study and a Phase 2 SLE study were included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A two\u2010compartment model with first order absorption and linear elimination and a mechanism\u2010based indirect response model adequately described the PK and PK\/PD relationships, respectively. Central compartment volume of distribution (<jats:italic>Vc<\/jats:italic>) positively correlated with body weight. Clearance (<jats:italic>CL<\/jats:italic>) negatively correlated with baseline albumin concentration and positively correlated with baseline CRP and creatinine clearance, and was slightly lower in females. After correcting for covariates, <jats:italic>CL<\/jats:italic> in CD subjects was approximately 60% higher than other populations. Maximum inhibition of PF\u201004236921 on CRP production (<jats:italic>I<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub>) negatively correlated with baseline albumin. <jats:italic>I<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub> positively correlated with baseline CRP and the relationship was captured as a covariance structure in the PK\/PD model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Integrated population PK and PK\/PD models of PF\u201004236921 have been developed using pooled data from healthy subjects and autoimmune patients. The current model enables simulation of PF\u201004236921 PK and PD profiles under various dosing regimens and patient populations and should facilitate future clinical study of PF\u201004236921 and other anti\u2010interleukin\u20106 monoclonal antibodies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13641","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T23:34:38Z","timestamp":1526686478000},"page":"2059-2074","source":"Crossref","is-referenced-by-count":16,"title":["Pharmacokinetics and C\u2010reactive protein modelling of anti\u2010interleukin\u20106 antibody (PF\u201004236921) in healthy volunteers and patients with autoimmune disease"],"prefix":"10.1111","volume":"84","author":[{"given":"Cheryl","family":"Li","sequence":"first","affiliation":[{"name":"Clinical Pharmacology\/Pharmacometrics, Clinical Research Pfizer Inc.  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Shoji","sequence":"additional","affiliation":[{"name":"Pharmacometrics\/Clinical Pharmacology, Clinical Research Pfizer Japan Inc.  Yoyogi, Shibuya\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Beebe","sequence":"additional","affiliation":[{"name":"Clinical Research Pfizer Inc.  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21552"},{"key":"e_1_2_8_3_1","first-page":"gutjnl\u20102017\u2010314","article-title":"Randomised trial and open\u2010label extension study of an anti\u2010interleukin\u20106 antibody in Crohn's disease (ANDANTE I and II)","author":"Danese S","year":"2017","journal-title":"Gut"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568010033484296"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.03.023"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-eular.724"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209668"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00054725-200409000-00026"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0361-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.328"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2581"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.03964.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.121"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.11.003"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000012998.04442.1f"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/11535960-000000000-00000"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9133-0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13876"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20178"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.170"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/11531280-000000000-00000"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0797-637"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.1.346"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-009-0718-4"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13243"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12850"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008329556"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.148"},{"key":"e_1_2_8_31_1","first-page":"197","article-title":"Evaluation of intestinal clearance and faecal excretion of alpha 1\u2010antiproteinase and immunoglobulins during Crohn's disease and ulcerative colitis","volume":"30","author":"Kapel N","year":"1992","journal-title":"Eur J Clin Chem Clin Biochem"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2585"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.64"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13641","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T11:33:44Z","timestamp":1695036824000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,25]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1111\/bcp.13641"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13641","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,25]]}}}