{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:17:10Z","timestamp":1783343830867,"version":"3.54.6"},"reference-count":25,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Perfusion"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The effect of the anticoagulant, dabigatran, and its antagonist, idarucizumab, on coagulation remains poorly quantified. There are few pharmacokinetic-pharmacodynamic data available to describe the interaction in humans or animals undergoing cardiopulmonary bypass.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Six sheep were given intravenous dabigatran infusion while undergoing cardiopulmonary bypass. Blood samples were collected for thromboelastographic reaction time (R-time) and drug assay at 1. 5, 15, 30, 60, 90, and 120\u00a0min after starting dabigatran. Further reaction times were measured at 1\u00a0min, 5\u00a0min, 15\u00a0min, 60\u00a0min, 4\u00a0h and 24\u00a0h after initiation of idarucizumab infusion. Plasma dabigatran concentrations, the dabigatran- idarucizumab interaction and R-times were analyzed using an integrated pharmacokinetic-pharmacodynamic model with non-linear mixed effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A 2-compartment model described dabigatran pharmacokinetics with a clearance (CL 0.0509\u00a0L\/min\/70\u00a0kg), intercompartment clearance (Q 0.229\u00a0L\/min\/70\u00a0kg), central volume of distribution (V1 3.89\u00a0L\/70\u00a0kg), peripheral volume of distribution (V2 11.4\u00a0L\/70\u00a0kg). The peripheral volume was 2.25 times larger during bypass. The effect compartment model estimates for an E\n                      <jats:sub>MAX<\/jats:sub>\n                      model using reaction time had an effect site concentration (Ce\n                      <jats:sub>50<\/jats:sub>\n                      40.8\u00a0mg\/L) eliciting half of the maximal effect (E\n                      <jats:sub>MAX<\/jats:sub>\n                      180\u00a0min). A potency factor for the antagonist, idarucizumab (EA\n                      <jats:sub>50<\/jats:sub>\n                      29.9\u00a0mg\/L), moved the dabigatran response relationship to the left.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dabigatran reversibly binds to the active site on the thrombin molecule, preventing activation of coagulation factors. Expansion of peripheral volume of distribution of dabigatran was observed during cardiopulmonary bypass, contributing to observed concentrations lower than predicted. A competitive interaction model adequately described dabigatran reversal by idarucizumab. These data and consequent parameter estimates inform future clinical studies in both animals and humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02676591251406086","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T22:51:31Z","timestamp":1764629491000},"page":"658-664","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dabigatran-idarucizumab pharmacokinetics-pharmacodynamics in sheep undergoing cardiopulmonary bypass"],"prefix":"10.1177","volume":"41","author":[{"given":"Michael P","family":"Eaton","sequence":"first","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiy M","family":"Nadtochiy","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsiana","family":"Stefanos","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-3019","authenticated-orcid":false,"given":"Brian J","family":"Anderson","sequence":"additional","affiliation":[{"name":"University of Auckland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/MAT.0000000000001652"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14476"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/pan.14511"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000004537"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/02676591231226291"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199529050-00001"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2001.00971.x"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000005580"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000012998.04442.1f"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23574"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.122"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-021-09788-3"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094708"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/50.11.1113"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-020-01439-2"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1177013815"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.599626"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1502000"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13181-011-0178-y"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/1076029609343004"},{"key":"e_1_3_7_22_2","first-page":"245","article-title":"Cardiac surgery in a patient with heparin-induced thrombocytopenia--cautions with use of the direct thrombin inhibitor, argatroban","volume":"70","author":"Kurup V","year":"2006","unstructured":"Kurup V, Transue S, Wu Y, et al. Cardiac surgery in a patient with heparin-induced thrombocytopenia--cautions with use of the direct thrombin inhibitor, argatroban. 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