{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:40:19Z","timestamp":1789893619916,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,15]],"date-time":"2013-03-15T00:00:00Z","timestamp":1363305600000},"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":[[2013,4]]},"abstract":"\n Aim<\/jats:title>\n \n To investigate the effect of the\n P<\/jats:styled-content>\n \u2010glycoprotein inhibitor verapamil on the pharmacokinetics and pharmacodynamics of dabigatran etexilate (\n DE<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n \n In this two part multiple crossover trial in 40 healthy subjects,\n DE<\/jats:styled-content>\n 150\u2009mg was given alone or with verapamil at different doses, duration of treatment (single\n vs.<\/jats:italic>\n multiple dosing), formulations, and timings (before, concurrently or after\n DE<\/jats:styled-content>\n ). Primary pharmacokinetic endpoints were determined from concentrations of total dabigatran (unconjugated plus conjugated). Pharmacodynamic endpoints were determined from clotting time.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The greatest effect was observed with single dose verapamil 120\u2009mg immediate release given 1\u2009h before single dose\n DE<\/jats:styled-content>\n . Geometric mean area under the plasma concentration curve [\n AUC<\/jats:styled-content>\n (0,\u221e)] and maximum analyte concentration in the plasma (\n \n C<\/jats:styled-content>\n <\/jats:italic>\n max<\/jats:sub>\n ) were increased by 143% [90% confidence interval (\n CI<\/jats:styled-content>\n ) 91, 208] and 179% (90%\n CI<\/jats:styled-content>\n 115, 262), respectively. The effect was reduced to a 71% and 91% increase in\n AUC<\/jats:styled-content>\n and\n \n C<\/jats:styled-content>\n <\/jats:italic>\n max<\/jats:sub>\n , respectively, when\n DE<\/jats:styled-content>\n was administered with verapamil 240\u2009mg extended release. After multiple verapamil dosing,\n DE AUC<\/jats:styled-content>\n (0,\u221e) and\n \n C<\/jats:styled-content>\n <\/jats:italic>\n max<\/jats:sub>\n increases were 54% and 63%, respectively. However,\n DE<\/jats:styled-content>\n given 2\u2009h before verapamil increased\n DE AUC<\/jats:styled-content>\n (0,\u221e) and\n \n C<\/jats:styled-content>\n <\/jats:italic>\n max<\/jats:sub>\n by <20%. With regard to clotting prolongation, the dabigatran plasma concentration\u2013effect relationship was generally not affected by the co\u2010administration of verapamil. Concomitant administration of\n DE<\/jats:styled-content>\n and verapamil did not reveal any unexpected safety findings.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Verapamil increased\n DE<\/jats:styled-content>\n bioavailability, likely due to inhibition of\n P<\/jats:styled-content>\n \u2010glycoprotein. Our results suggest that an interaction between verapamil and\n DE<\/jats:styled-content>\n can be minimized if\n DE<\/jats:styled-content>\n is administered 2\u2009h prior to verapamil.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/j.1365-2125.2012.04453.x","type":"journal-article","created":{"date-parts":[[2012,9,5]],"date-time":"2012-09-05T05:27:11Z","timestamp":1346822831000},"page":"1053-1062","source":"Crossref","is-referenced-by-count":145,"title":["Oral bioavailability of dabigatran etexilate (\n P<\/scp>\n radaxa\n \u00ae<\/sup>\n ) after co\u2010medication with verapamil in healthy subjects"],"prefix":"10.1111","volume":"75","author":[{"given":"Sebastian","family":"H\u00e4rtter","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH Biberach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Sennewald","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH Biberach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Nehmiz","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH Biberach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Reilly","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals Ridgefield CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905561"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02748.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61445-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1586\/erc.11.21"},{"key":"e_1_2_9_6_1","unstructured":"FDA.Pradaxa label.2010. Available athttp:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2011\/022512s007lbl.pdf(last accessed 18 May 2012)."},{"key":"e_1_2_9_7_1","unstructured":"Pradax\u00ae monograph.Canada: Boehringer Ingelheim 2012. Available athttp:\/\/www.boehringer\u2010ingelheim.ca\/content\/dam\/internet\/opu\/ca_EN\/documents\/humanhealth\/product_monograph\/Pradax\u2010pm.pdf(last accessed 18 May 2012)."},{"key":"e_1_2_9_8_1","unstructured":"PharmPro.Boehringer Ingelheim: PRAZAXA (dabigatran etexilate) approved in Japan for stroke prevention in atrial fibrillation.2011. Available athttp:\/\/www.pharmpro.com\/News\/Feeds\/2011\/01\/pharmaceutical\u2010companies\u2010boehringer\u2010ingelheim\u2010prazaxa\u2010dabigatran\u2010etexilate\u2010approved\u2010in\u2010japan\u2010\/(last accessed 20 September 2012)."},{"key":"e_1_2_9_9_1","unstructured":"Pradaxa Summary of Products Characteristics.European Medicine Agency 2012. Available athttp:\/\/www.medicines.org.uk\/emc\/medicine\/20760(last accessed 18 May 2011)."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.28.11.1354"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200847050-00001"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.019083"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029609343004"},{"key":"e_1_2_9_14_1","unstructured":"H\u00e4rtterS SennewaldR RathgenK NehmizG ReillyPA.Increase in the oral bioavailability of dabigatran etexilate (Pradaxa\u00ae) after co\u2010medication with verapamil.2011. Presented at the 112th American Society for Clinical Pharmacology and Therapeutics (ASCPT) 2\u20135 March 2011; Dallas Texas."},{"key":"e_1_2_9_15_1","unstructured":"Advisory Committee Briefing Document.Dabigatran etexilate. Boehringer Ingelheim 2010. Available athttp:\/\/www.fda.gov\/downloads\/AdvisoryCommittees\/CommitteesMeetingMaterials\/Drugs\/CardiovascularandRenalDrugsAdvisoryCommittee\/UCM226009.pdf(last accessed 4 April 2011)."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-09-0659"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","DOI":"10.1201\/9781420036091","volume-title":"Design and Analysis of Cross\u2010Over Trials, Second Edition","author":"Jones B","year":"2003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-11-0758"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(02)00171-0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342010-00003"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2004.05.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2005.11.001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.08.026"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1007378"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2125.2012.04453.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2125.2012.04453.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:05:45Z","timestamp":1697414745000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2125.2012.04453.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,15]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1111\/j.1365-2125.2012.04453.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2125.2012.04453.x","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,15]]}}}