{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:16:30Z","timestamp":1791015390380,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T00:00:00Z","timestamp":1390867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Ofatumumab is a human monoclonal antibody directed at CD20 approved for treatment of chronic lymphocytic leukemia. The population pharmacokinetics of intravenous ofatumumab were characterized in patients with relapsed\/refractory chronic lymphocytic leukemia, relapsed\/refractory follicular lymphoma, and rheumatoid arthritis, diseases with widely varying CD20\n                      <jats:sup>+<\/jats:sup>\n                      B\u2010cell counts in blood. Serum concentration data from a total of 477 patients who received ofatumumab doses ranging from 100\u2009mg to 2000\u2009mg in different dosing regimens were analyzed to determine the pharmacokinetic characteristics of ofatumumab across different patient groups and to identify factors contributing to the pharmacokinetic variability. Ofatumumab pharmacokinetics were well described by a linear two\u2010compartment model component to represent non\u2010specific monoclonal antibody clearance from the central compartment interacting with a model component representing the target\u2010mediated clearance of ofatumumab by binding to CD20 expressed on B cells. The clearance (7.5\u2009mL\/h) and steady\u2010state volume of distribution (5.3\u2009L) for the linear, non\u2010specific component were consistent with results obtained for other monoclonal antibodies. The target\u2010mediated clearance component was related to the disease\u2010specific number of circulating B cells, which will allow simulation of the contribution of target\u2010mediated clearance to ofatumumab pharmacokinetics in untested disease states with data on B\u2010cell counts and turnover.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcph.268","type":"journal-article","created":{"date-parts":[[2014,1,20]],"date-time":"2014-01-20T00:58:41Z","timestamp":1390179521000},"page":"818-827","source":"Crossref","is-referenced-by-count":33,"title":["Population pharmacokinetics of ofatumumab in patients with chronic lymphocytic leukemia, follicular lymphoma, and rheumatoid arthritis"],"prefix":"10.1002","volume":"54","author":[{"given":"Herbert","family":"Struemper","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation GlaxoSmithKline Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sale","sequence":"additional","affiliation":[{"name":"Next Level Solutions LLC Raleigh NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation GlaxoSmithKline King of Prussia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"Copenhagen Center for Arthritis Research Copenhagen University Hospital at Glostrup and Department of Clinical Medicine, University of Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"\u00d6sterborg","sequence":"additional","affiliation":[{"name":"Department of Hematology Karolinska University Hospital Solna Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Wierda","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center The University of Texas Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Hagenbeek","sequence":"additional","affiliation":[{"name":"Department of Hematology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Coiffier","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'H\u00e9matologie Centre Hospitalier Lyon Sud Pierre\u2010Benite Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanne C.","family":"Jewell","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation GlaxoSmithKline Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.362"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830400404"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-01-0039"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-111781"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08193.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.3187"},{"key":"e_1_2_8_8_1","first-page":"921","article-title":"Final analysis from the international trial of single\u2010agent ofatumumab in patients with fludarabine\u2010refractory chronic lymphocytic leukemia","volume":"116","author":"Wierda WG","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-117671"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27524"},{"key":"e_1_2_8_11_1","volume-title":"American Conference on Pharmacometrics (ACoP)","author":"Sale M","year":"2011"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2165\/11535960-000000000-00000"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07348.x"},{"key":"e_1_2_8_15_1","first-page":"1","article-title":"Metabolism of immunoglobulins","volume":"13","author":"Waldmann TA","year":"1969","journal-title":"Prog. Allerg"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1995.tb08411.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9458-6"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106279"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.104"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-011-0615-2"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.thj.6200119"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005277075"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.268","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T17:49:57Z","timestamp":1696355397000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,28]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1002\/jcph.268"],"URL":"https:\/\/doi.org\/10.1002\/jcph.268","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,28]]}}}