{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:03:37Z","timestamp":1784955817697,"version":"3.55.0"},"reference-count":68,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thromboembolic diseases, including venous thromboembolism and atrial fibrillation\u2013related stroke, represent a prevalent health concern and a risk for mortality and health care costs. Rivaroxaban is a direct oral factor Xa inhibitor that is used as an anticoagulant to prevent thromboembolism; although it had a predictable pharmacokinetic profile, it had great inter\u2010individual variability, where some experienced inadequate response and recurrent thrombosis, and others were subjected to bleeding risks. Genetic polymorphisms that could impact the pharmacokinetics and\/or pharmacodynamics of rivaroxaban should be involved in its dose adjustment.<\/jats:p>\n                  <jats:p>The present work highlighted the current pharmacogenomics evidences influencing rivaroxaban therapy with an analysis of data from previous reports. Using reliable pharmacogenomic profiles can reduce the adverse effects of rivaroxaban and improve patient outcomes in the future.<\/jats:p>\n                  <jats:p>\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    and\n                    <jats:italic>CYP3A5<\/jats:italic>\n                    polymorphisms greatly impacted the pharmacokinetics of rivaroxaban;\n                    <jats:italic>CYP2J2<\/jats:italic>\n                    polymorphisms were not greatly associated with the clinical outcome. Genetic polymorphisms in membrane transporters like\n                    <jats:italic>ABCB1<\/jats:italic>\n                    and\n                    <jats:italic>ABCG2<\/jats:italic>\n                    could modulate the distribution and absorption of rivaroxaban, leading to inter\u2010individual variation in response. Furthermore, novel genetic polymorphisms in\n                    <jats:italic>SUSD3<\/jats:italic>\n                    and\n                    <jats:italic>APOB<\/jats:italic>\n                    were associated with bleeding risk during rivaroxaban therapy. A preliminary effect of polymorphisms in\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    ,\n                    <jats:italic>PRF1<\/jats:italic>\n                    , and\n                    <jats:italic>PRKAG2<\/jats:italic>\n                    on rivaroxaban outcome still needs validation. Both pharmacogenomic analysis (\n                    <jats:italic>CYP3A4\/5, ABCB1, and ABCG2<\/jats:italic>\n                    ) and drug interactions data could guide dose adjustments of rivaroxaban and significantly decrease the major bleeding risks clinically.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70236","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:28:52Z","timestamp":1783056532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New Insights into Genetic Polymorphisms Influencing the Therapeutic Efficacy and Toxicity of Rivaroxaban"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-1517","authenticated-orcid":false,"given":"Mohammad","family":"Salem Hareedy","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine Assiut University  Assiut Egypt"},{"name":"Department of Pharmacology Faculty of Medicine Mutah University  Karak Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayan W.","family":"Mubaideen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Mutah University  Karak Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana O.","family":"Al Tarawneh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Mutah University  Karak Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saif A.","family":"Abu Ghaida","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Mutah University  Karak Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer F.","family":"Zayed","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Mutah University  Karak Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameeh","family":"Al\u2010Sarayreh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Faculty of Medicine Mutah University  Al\u2010Karak Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abulmaaty M.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology Faculty of Medicine Mutah University  Mutah Jordan"},{"name":"Department of Anatomy and Embryology Faculty of Medicine Benha University  Benha Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Kamel","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Assiut University  Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef M.","family":"Al\u2010Saraireh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine Mutah University  Karak Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulaiman Mohammed","family":"Alnasser","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy Qassim University  Buraydah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.3.229"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2015.11.033"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2013.04.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.15420\/ecr.2017:11:2"},{"issue":"3","key":"e_1_2_9_6_1","first-page":"199","article-title":"Prophylaxis of venous thromboembolism: low molecular weight heparin compared to the selective anticoagulants rivaroxaban, dabigatran and fondaparinux","volume":"30","author":"Welzel D","year":"2011","journal-title":"Int Angiol"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203315611495"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472\u20108206.2011.00981.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjqcco\/qcy040"},{"key":"e_1_2_9_10_1","volume-title":"StatPearls","author":"Singh R","year":"2026"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2327"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9589036"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2025.00206"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mjafi.2016.11.013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1574949"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010019\u201002639\u20108"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.202978"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477\u20109560\u201011\u201011"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2012.04181.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477\u20109560\u201012\u201022"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010013\u20100100\u20107"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9050451"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010013\u20100174\u20104"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557\u2010020\u201007129\u2010z"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V110.11.1880.1880"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2009.03390.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm9010007"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11010037"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v14.i1.40"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/17539447241249886"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.178049"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557\u2010023\u201007495\u20104"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina60101712"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40292\u2010019\u201000342\u20104"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13488"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.124.040698"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010025\u201003821\u2010x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.914842"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2025.2522731"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414\u2010431X2024e13257"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000483"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S417096"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246\u2010023\u201000506\u20103"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13577"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2145"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2316"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14091889"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.2147\/PGPM.S234910"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.11310"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S534569"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2024.02.009"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmacy11010029"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.089680"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010024\u201001358\u20103"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.4314\/ahs.v24i1.36"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102710.2009.01127.x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/48.10.1668"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12090898"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.121.007956"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.70050"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1R055"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010014\u20100278\u20105"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2255"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13082277"},{"key":"e_1_2_9_65_1","volume-title":"StatPearls","author":"Amaraneni A","year":"2026"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2023.07.008"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59010181"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1189976"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2019.12.021"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70236","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70236","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:47:38Z","timestamp":1784954858000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":68,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jcph.70236"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70236","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-03-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70236"}}