{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:06:13Z","timestamp":1783397173483,"version":"3.54.6"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T00:00:00Z","timestamp":1442275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fostamatinib is a tyrosine kinase inhibitor with activity against spleen tyrosine kinase which has completed clinical trials for patients with rheumatoid arthritis. In clinical studies fostamatinib treatment was associated with a small elevation of systemic arterial blood pressure (<jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>), a similar finding to that seen with other kinase inhibitors, especially those that inhibit <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>2 signaling. We have investigated the link between fostamatinib\u2010induced blood pressure elevation and plasma levels of the fostamatinib\u2010active metabolite R940406 in conscious rats and found the time course of the <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> effect correlated closely with changes in R940406 plasma concentration, indicating a direct pharmacological relationship. Free plasma levels of R940406 produced in these studies (up to 346\u00a0nmol\/L) span the clinically observed mean peak free plasma concentration of 49\u00a0nmol\/L. We have demonstrated that the blood pressure elevation induced by fostamatinib dosing can be successfully controlled by a variety of methods, notably simple drug withdrawal or codosing with a range of standard antihypertensive agents such as atenolol, captopril, and nifedipine. These findings support potential methods of maintaining patient safety while on fostamatinib therapy. Furthermore, we have demonstrated, using nifedipine as an example agent, that this blood pressure control was not achieved by reduction in plasma exposure of R940406, suggesting that potential benefits from the pharmacology of the investigational drug can be maintained while blood pressure control is managed by use of standard comedications.<\/jats:p>","DOI":"10.1002\/prp2.176","type":"journal-article","created":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T17:51:32Z","timestamp":1442339492000},"source":"Crossref","is-referenced-by-count":12,"title":["Prevention of fostamatinib\u2010induced blood pressure elevation by antihypertensive agents"],"prefix":"10.1002","volume":"3","author":[{"given":"Dave","family":"Lengel","sequence":"first","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Lamm Bergstr\u00f6m","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herb","family":"Barthlow","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Oldman","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Musgrove","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Harmer","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"Valentin","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Duffy","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Braddock","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Curwen","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Alderley Park Macclesfield Cheshire SK10 4TG United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90502.2008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/0284186X.2010.543696"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.109058"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.776831"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4783"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1990"},{"key":"e_1_2_8_8_1","first-page":"S198","article-title":"OSKIRA\u20102: a phase III, multicenter, randomized, double\u2010blind, placebo\u2010controlled parallel\u2010group study of 2 dosing regimens of fostamatinib in rheumatoid arthritis patients with an inadequate response to disease\u2010modifying antirheumatic drugs","volume":"65","author":"Dawes P","year":"2013","journal-title":"Arth Rheum"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.2066"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30114"},{"key":"e_1_2_8_11_1","first-page":"S199","article-title":"OSKIRA\u20103 OSKIRA\u20103: a phase III, multicenter, randomized, double\u2010blind, placebo\u2010controlled parallel\u2010group study of 2 dosing regimens of fostamatinib in rheumatoid arthritis patients with an inadequate response to a tumor necrosis factor \u2010\u03b1 antagonist","volume":"65","author":"Genovese MC","year":"2013","journal-title":"Arth Rheum"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds179"},{"key":"e_1_2_8_13_1","volume-title":"\u201cLeast square Means in the Fixed Effects General Linear Model\u201d SAS Technical Report R\u2010103","author":"Goodnight JH","year":"1978"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533558"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2014.08.013"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.2273"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.530"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2013.788642"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-166439"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2806"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12029-009-9104-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1093\/annonc\/mdn637","article-title":"Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first\u2010time bevacizumab","volume":"29","author":"Scartozzi M","year":"2009","journal-title":"Ann Oncol"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.5.1215"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-013-0050-x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.5740"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12559"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.2165\/11590180-000000000-00000"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1000500"},{"key":"e_1_2_8_29_1","first-page":"S763","article-title":"OSKIRA\u20101: a phase III, multicenter, randomized, double\u2010blind, placebo\u2010controlled parallel\u2010group study of 2 dosing regimens of fostamatinib in rheumatoid arthritis patients with an inadequate response to methotrexate","volume":"65","author":"Weinblatt M","year":"2013","journal-title":"Arth Rheum"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.13.7.743"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/02841860802314720"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.176","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.176","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T15:54:44Z","timestamp":1696175684000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,15]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1002\/prp2.176"],"URL":"https:\/\/doi.org\/10.1002\/prp2.176","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,15]]},"article-number":"e00176"}}