{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T17:05:25Z","timestamp":1774112725286,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T00:00:00Z","timestamp":1512000000000},"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":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pharmacokinetics and antithrombotic effects of the Factor Xa inhibitor rivaroxaban were studied in subjects with mild renal insufficiency concurrently taking the P\u2010glycoprotein and moderate CYP3A inhibitor verapamil, a drug commonly administered to patients with hypertension, ischemic heart disease, or atrial fibrillation. Age\u2010matched controls with normal renal function were studied concurrently. Subjects\u2019 overall mean age was 59 years. Mean creatinine clearance values in the 2 groups were 105 and 71 mL\/min. After single 20\u2010mg oral doses, rivaroxaban area under the curve (AUC) was increased by a factor of 1.11 (ratio of geometric means [RGM]) in mild renal insufficiency compared to controls. Verapamil coadministration independently increased AUC to the same extent in both the mild renal insufficiency and control groups (RGM, 1.39 and 1.43). Concurrent mild renal insufficiency and verapamil produced additive inhibition compared to controls without verapamil (RGM, 1.58). Prothrombin time (PT) prolongation and Factor Xa inhibition tracked plasma rivaroxaban, and were enhanced by verapamil. Concentration\u2013response relationships for PT (linear) and Factor Xa inhibition (hyperbolic) were unaffected by renal function or verapamil. The absolute and relative increases in rivaroxaban AUC caused by verapamil in mild renal insufficiency subjects are potentially associated with an increased bleeding risk. Modification of recommended dosage may be required in this combination of circumstances to reduce risk to patients.<\/jats:p>","DOI":"10.1002\/jcph.1040","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T23:42:52Z","timestamp":1512085372000},"page":"533-540","source":"Crossref","is-referenced-by-count":42,"title":["Impaired Rivaroxaban Clearance in Mild Renal Insufficiency With Verapamil Coadministration: Potential Implications for Bleeding Risk and Dose Selection"],"prefix":"10.1002","volume":"58","author":[{"given":"David J.","family":"Greenblatt","sequence":"first","affiliation":[{"name":"Tufts University School of Medicine  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maulik","family":"Patel","sequence":"additional","affiliation":[{"name":"Emerald Lake Safety LLC  Newport Beach CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerold S.","family":"Harmatz","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne T.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine  Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Rubino","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics  Buffalo NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina R.","family":"Chow","sequence":"additional","affiliation":[{"name":"Emerald Lake Safety LLC  Newport Beach CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-012-0030-9"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S45644"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60243-4"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2016.05.002"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-015-1314-3"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2012.19"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0100-7"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12387"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.025551"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.025569"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.073890"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12075"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03753.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.352"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025092829696"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122010609"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920008784220664"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2004.04.006"},{"key":"e_1_2_5_20_1","unstructured":"Symphony Health Patient Source Longitudinal Data Base.Data for the 12\u2010month period ending May 2017."},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006286904"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP45335"},{"key":"e_1_2_5_23_1","unstructured":"Center for Drug Research and Evaluation Food and Drug Administration. 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