{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:54:52Z","timestamp":1783385692548,"version":"3.54.6"},"reference-count":32,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Perfusion"],"published-print":{"date-parts":[[2025,1]]},"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 determine dabigatran dose in humans or animals undergoing cardiopulmonary bypass.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Five sheep were given intravenous dabigatran 4\u00a0mg\/kg. Blood samples were collected for thromboelastometric reaction time (R-time) and drug assay at 5, 15, 30, 60, 120, 240, 480\u00a0min, and 24\u00a0h. Plasma dabigatran concentrations and R-times were analyzed using an integrated pharmacokinetic-pharmacodynamic model using non-linear mixed effects. The impact of idarucizumab 15\u00a0mg\/kg administered 120\u00a0min after dabigatran 4\u00a0mg\/kg and its effect on R-time was observed.<\/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 0.0453\u00a0L\/min\/70\u00a0kg), intercompartment clearance (Q 0.268\u00a0L\/min\/70\u00a0kg), central volume of distribution (V1 2.94\u00a0L\/70\u00a0kg), peripheral volume of distribution (V2 9.51\u00a0L\/70\u00a0kg). The effect compartment model estimates for a sigmoid 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                      64.2\u00a0mg\/L) eliciting half of the maximal effect (E\n                      <jats:sub>MAX<\/jats:sub>\n                      180\u00a0min). The plasma-effect compartment equilibration half time (T\n                      <jats:sub>1\/2<\/jats:sub>\n                      keo) was 1.04\u00a0min. Idarucizumab 15\u00a0mg\/kg reduced R-time by approximately 5\u00a0min.\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. The pharmacologic target concentration strategy uses pharmacokinetic-pharmacodynamic information to inform dose. A loading dose of dabigatran 0.25\u00a0mg\/kg followed by a maintenance infusion of dabigatran 0.0175\u00a0mg\/kg\/min for 30\u00a0min and a subsequent infusion dabigatran 0.0075\u00a0mg\/kg\/min achieves a steady state target concentration of 5\u00a0mg\/L in a sheep model.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02676591231226291","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T19:15:17Z","timestamp":1704309317000},"page":"183-191","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dabigatran pharmacokinetic-pharmacodynamic in sheep: Informing dose for anticoagulation during cardiopulmonary bypass"],"prefix":"10.1177","volume":"40","author":[{"given":"Michael P","family":"Eaton","sequence":"first","affiliation":[{"name":"University of Rochester Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiy M","family":"Nadtochiy","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsiana","family":"Stefanos","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center, New York, NY, USA"}],"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":"Department Anesthesiology, University of Auckland, Auckland, New 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