Evaluation of the Efficacy and Safety of Rivaroxaban Using a Computer Model for Blood Coagulation
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{"title"=>"Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation", "type"=>"journal", "authors"=>[{"first_name"=>"Rolf", "last_name"=>"Burghaus", "scopus_author_id"=>"6506432096"}, {"first_name"=>"Katrin", "last_name"=>"Coboeken", "scopus_author_id"=>"35309587400"}, {"first_name"=>"Thomas", "last_name"=>"Gaub", "scopus_author_id"=>"37113660000"}, {"first_name"=>"Lars", "last_name"=>"Kuepfer", "scopus_author_id"=>"56095324700"}, {"first_name"=>"Anke", "last_name"=>"Sensse", "scopus_author_id"=>"57199347721"}, {"first_name"=>"Hans Ulrich", "last_name"=>"Siegmund", "scopus_author_id"=>"55816177600"}, {"first_name"=>"Wolfgang", "last_name"=>"Weiss", "scopus_author_id"=>"56678977700"}, {"first_name"=>"Wolfgang", "last_name"=>"Mueck", "scopus_author_id"=>"12808211500"}, {"first_name"=>"Joerg", "last_name"=>"Lippert", "scopus_author_id"=>"8268165900"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0017626", "sgr"=>"79955547867", "issn"=>"19326203", "pui"=>"361682397", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "pmid"=>"21526168", "scopus"=>"2-s2.0-79955547867"}, "id"=>"16bae51d-626e-30a7-9425-2ce59d64417a", "abstract"=>"Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.", "link"=>"http://www.mendeley.com/research/evaluation-efficacy-safety-rivaroxaban-using-computer-model-blood-coagulation", "reader_count"=>48, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Researcher"=>12, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>4, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Researcher"=>12, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>4, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Mathematics"=>4, "Medicine and Dentistry"=>25, "Agricultural and Biological Sciences"=>9, "Design"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>25}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Computer Science"=>{"Computer Science"=>1}, "Mathematics"=>{"Mathematics"=>4}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"Colombia"=>1, "Netherlands"=>1, "Slovenia"=>1, "Switzerland"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/781449"], "description"=>"<p>(A) rivaroxaban (experimental data from internal studies); (B) DX-9065a\n (experimental data from the literature <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Ieko1\" target=\"_blank\">[30]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Murayama1\" target=\"_blank\">[31]</a>,\n <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Kappert1\" target=\"_blank\">[41]</a>; and (C) ximelagatran (experimental data for\n PT and aPTT from the literature <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Mattsson2\" target=\"_blank\">[36]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Eriksson1\" target=\"_blank\">[37]</a>.\n aPTT, activated partial thromboplastin time; INR, international\n normalized ratio; PT, prothrombin time.</p>", "links"=>[], "tags"=>["aptt", "plasma", "anticoagulant"], "article_id"=>451809, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g006", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PT_and_aPTT_dependent_on_plasma_concentration_of_anticoagulant____drugs_/451809", "title"=>"PT and aPTT dependent on plasma concentration of anticoagulant\n drugs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:30:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/781291"], "description"=>"<p>(A) published PT INR data from Fisher Diagnostics 1999 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Fisher1\" target=\"_blank\">[40]</a>\n and with (B) published aPTT data from Kappert 2002 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Kappert1\" target=\"_blank\">[41]</a>. Reagents used in aPTT reference studies:\n Pathromtin® SL (SL; Behringwerke AG, Marburg, Germany) and\n Behring Coagulation Time (BCT). aPTT, activated partial\n thromboplastin time; INR, international normalized ratio; PT,\n prothrombin time.</p>", "links"=>[], "tags"=>["coagulation", "variations", "with", "published"], "article_id"=>451652, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Simulation_of_coagulation_factor_variations_and_comparison_with_____published_experimental_data_/451652", "title"=>"Simulation of coagulation factor variations and comparison with\n published experimental data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:27:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/780826"], "description"=>"<p>Targets for anticoagulant drugs in the coagulation pathway <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Haas1\" target=\"_blank\">[<b>57</b>]</a>.</p>", "links"=>[], "tags"=>["anticoagulant", "drugs", "coagulation", "pathway"], "article_id"=>451185, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g001", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Targets_for_anticoagulant_drugs_in_the_coagulation_pathway_57_/451185", "title"=>"Targets for anticoagulant drugs in the coagulation pathway [<b>57</b>].", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:19:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/781707"], "description"=>"<p>Rivaroxaban concentrations at 20 mg once daily: C<sub>max</sub> 251\n ng/ml, C<sub>trough</sub> 30 ng/ml. The width of the rivaroxaban\n curve reflects the C<sub>trough</sub> to C<sub>max</sub>\n concentration range and the width of the warfarin curve reflects the\n typically used INR range. C<sub>max</sub>, maximum concentration;\n C<sub>trough</sub>, minimum concentration; INR, international\n normalized ratio; OD, once daily; TF, tissue factor.</p>", "links"=>[], "tags"=>["thrombus", "inhibition", "rivaroxaban", "and"], "article_id"=>452072, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g008", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Simulation_of_thrombus_inhibition_with_rivaroxaban_and_____warfarin_/452072", "title"=>"Simulation of thrombus inhibition with rivaroxaban and\n warfarin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:34:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/781086"], "description"=>"<p>The dashed line and dots and the dotted line and the diamonds indicate\n the spread of the threshold for blood flow- and diffusion-mediated\n washout of a clot formation (α<sub>crit</sub>, seconds; <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#s2\" target=\"_blank\">Methods</a>) within the therapeutic\n concentration range (difference between C<sub>trough</sub> and\n C<sub>max</sub>); α<sub>crit</sub> at C<sub>mean</sub> is\n indicated by the solid line and crosses. The strong extrinsic trigger\n (TF 10<sup>−11</sup> mol/l, seconds; <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone-0017626-t003\" target=\"_blank\">Table 3</a>) is considered as safety\n relevant (A). The (red) shaded area indicates safety-relevant\n prolongation of clotting times above the effect of warfarin titrated to\n an INR of 3, which is used as a safety reference. All therapies above\n the level of this therapy are considered safe. The other three triggers\n (B: Factor XIIa 10<sup>−11</sup> mol/l; C: TF\n 10<sup>−14</sup> mol/l; D: 10<sup>−14</sup> mol/l) are\n considered as efficacy relevant. The effect of warfarin titrated to an\n INR of 1.5 is used as an efficacy reference and all therapies reaching\n inhibition above the level of this therapy, i.e. α<sub>crit</sub>\n values below the reference level (green shaded area) are considered\n efficacious. BD, twice daily; C<sub>max</sub>, maximum concentration;\n C<sub>mean</sub>, mean concentration; C<sub>trough</sub>, minimum\n concentration; INR, international normalized ratio; IV, intravenous; OD,\n once daily; TF, tissue factor.</p>", "links"=>[], "tags"=>["anticoagulants", "thresholds", "blood", "flow-mediated", "washout", "physiologically", "plausible", "trigger"], "article_id"=>451435, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g003", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Benchmarking_of_anticoagulants_based_on_thresholds_for_blood____flow_mediated_washout_using_physiologically_plausible_trigger____concentrations_/451435", "title"=>"Benchmarking of anticoagulants based on thresholds for blood\n flow-mediated washout using physiologically plausible trigger\n concentrations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:23:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/781840"], "description"=>"<p>This graph shows the effect of increasing concentration of\n rivaroxaban on thrombin peak height for a\n 5×10<sup>−12</sup> mol/l tissue factor trigger\n (dilution 2∶3, 4 µM phospholipid, corresponding to an\n <i>in silico</i> thrombin generation assay). To\n compare this with warfarin therapy, the corresponding values for\n INRs (1.5–4.0) are marked by vertical lines. The ranges for\n C<sub>max</sub>, C<sub>mean</sub> and C<sub>trough</sub> reflect\n experimental rivaroxaban values found in dose-finding studies <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Eriksson2\" target=\"_blank\">[48]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Eriksson3\" target=\"_blank\">[50]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Agnelli1\" target=\"_blank\">[55]</a>. The simulated thrombin peak reduction is\n in the range of therapeutically used INRs. BD, twice daily;\n C<sub>max</sub>, maximum concentration; C<sub>mean</sub>, mean\n concentration; C<sub>trough</sub>, minimum concentration; INR,\n international normalized ratio; OD, once daily.</p>", "links"=>[], "tags"=>["rivaroxaban", "thrombin"], "article_id"=>452204, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g009", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_rivaroxaban_exposure_on_thrombin_peak_height_/452204", "title"=>"Effect of rivaroxaban exposure on thrombin peak height.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:36:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/782202"], "description"=>"<p>53 mg OD/BD doses (although not used in clinical studies) were\n simulated to double exposure (C<sub>mean</sub>) of 20 mg OD/BD,\n taking into account the less than dose-proportional increase in\n exposure due to reduced absorption, observed at high doses <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Kubitza1\" target=\"_blank\">[3]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Mueck1\" target=\"_blank\">[26]</a>. A control\n without any drugs was also run in the model. BD, twice daily;\n C<sub>max</sub>, maximum drug concentration; C<sub>mean</sub>,\n average drug concentration; C<sub>trough</sub>, minimum drug\n concentration; INR, international normalized ratio; IV, intravenous;\n OD, once daily; s.c., subcutaneous.</p>", "links"=>[], "tags"=>["dx-9065a", "and", "enoxaparin", "included"], "article_id"=>452562, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.t001", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regimens_for_rivaroxaban_warfarin_ximelagatran_DX_9065a_and____enoxaparin_included_in_the_model_/452562", "title"=>"Regimens for rivaroxaban, warfarin, ximelagatran, DX-9065a and\n enoxaparin included in the model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-22 00:42:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/781204"], "description"=>"<p>Simulation of a PT scenario, thrombin and fibrin generation. PT,\n prothrombin time.</p>", "links"=>[], "tags"=>["pt", "coagulation"], "article_id"=>451566, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Implementation_of_PT_into_in_vitro_coagulation_____scenarios_/451566", "title"=>"Implementation of PT into <i>in vitro</i> coagulation\n scenarios.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:26:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/782007"], "description"=>"<p>Error bars show the spread of the clotting time within the\n therapeutic concentration range (difference between\n C<sub>trough</sub> and C<sub>max</sub>); clotting time at\n C<sub>mean</sub> was used for the main bar. The strong extrinsic\n trigger (TF 10<sup>−11</sup> mol/l, seconds; <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone-0017626-t003\" target=\"_blank\">Table 3</a>) is\n considered as safety relevant (A). The (red) shaded area indicates\n safety-relevant prolongation of clotting times above the effect of\n warfarin titrated to an INR of 3, which is used as a safety\n reference. All therapies below the level of this therapy are\n considered safe. The other three triggers (B: Factor XIIa\n 10<sup>−11</sup> mol/l; C: TF 10<sup>−14</sup>\n mol/l; D: 10<sup>−14</sup> mol/l) are considered as efficacy\n relevant. The effect of warfarin titrated to an INR of 1.5 is used\n as an efficacy reference and all therapies reaching inhibition above\n the level of this therapy (green shaded area) are considered\n efficacious. BD, twice daily; C<sub>max</sub>, maximum\n concentration; C<sub>mean</sub>, mean concentration;\n C<sub>trough</sub>, minimum concentration; INR, international\n normalized ratio; i.v., intravenous; OD, once daily, TF, tissue\n factor.</p>", "links"=>[], "tags"=>["anticoagulants", "clotting", "times", "using", "physiologically", "plausible"], "article_id"=>452367, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g010", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Benchmarking_of_anticoagulants_based_on_clotting_times_using_____physiologically_plausible_trigger_concentrations_/452367", "title"=>"Benchmarking of anticoagulants based on clotting times using\n physiologically plausible trigger concentrations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:39:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/782164"], "description"=>"<p><i>In vivo</i> coagulation scenarios included in the\n model.</p>", "links"=>[], "tags"=>["coagulation", "scenarios", "included", "the"], "article_id"=>452520, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_coagulation_scenarios_included_in_the____model_/452520", "title"=>"<i>In vivo</i> coagulation scenarios included in the\n model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-22 00:42:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/781626"], "description"=>"<p>One control group (Control) without medication and three patient groups:\n mechanical (Mec) or biological (Bio) heart valve replacement with\n different co-medications (acetylsalicylic acid [ASA] or\n warfarin [War]) at different target INRs with model\n predictions of INRs <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017626#pone.0017626-Ferreira1\" target=\"_blank\">[47]</a>. Simulated INR values were based on\n measurements of the mean concentrations of Factors II, VII, X, protein C\n and protein S resulting from therapy. Factor IX was set to the average\n concentration of the measured factors. INR, international normalized\n ratio.</p>", "links"=>[], "tags"=>["simulated", "inr"], "article_id"=>451986, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g007", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_simulated_with_measured_INR_values_/451986", "title"=>"Comparison of simulated with measured INR values.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:33:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/391616", "https://ndownloader.figshare.com/files/391661", "https://ndownloader.figshare.com/files/391685"], "description"=>"<div><p>Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration–effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.</p> </div>", "links"=>[], "tags"=>["efficacy", "rivaroxaban", "computer", "coagulation"], "article_id"=>137332, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0017626.s001", "https://dx.doi.org/10.1371/journal.pone.0017626.s002", "https://dx.doi.org/10.1371/journal.pone.0017626.s003"], "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Evaluation_of_the_Efficacy_and_Safety_of_Rivaroxaban_Using_a_Computer___Model_for_Blood_Coagulation/137332", "title"=>"Evaluation of the Efficacy and Safety of Rivaroxaban Using a Computer\n Model for Blood Coagulation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-04-22 02:02:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/780926"], "description"=>"<p>The top equation represents the initial condition where the concentration\n of each species c<sub>j</sub> is the same for the coagulation zone\n ‘thromb’ and the reservoir ‘blood’. The first\n element of the bottom equation (‘coagulation kinetics’)\n represents the coagulation processes (i.e. the biochemical kinetics of\n the model), whereas the second element (‘coupling’)\n represents the flowing conditions. α, general coupling constant, as\n a function of blood flow and geometry (size of vessels); c<sub>j</sub>,\n concentration of coagulation factor; D<sub>j</sub>,\n diffusion–convection coefficient; F, blood coagulation cascade\n model coefficient.</p>", "links"=>[], "tags"=>["surgery", "Computational biology", "hematology", "computer science", "Biochemistry"], "article_id"=>451285, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Modelling_of_blood_flow_/451285", "title"=>"Modelling of blood flow.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-22 00:21:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/782120"], "description"=>"<p>Va, IIa, IXa, Xa and XIa denote activated coagulation factors.\n ATIII, antithrombin; BAY59-7939, rivaroxaban; fu, fraction\n unbound; Hep, heparin (here parameterized as enoxaparin); on,\n k<sub>on</sub>, association rate constant; mIIa,\n meizothrombin; Tm, thrombomodulin; Xim, ximelagatran active\n metabolite (melagatran).</p>", "links"=>[], "tags"=>["surgery", "Computational biology", "hematology", "computer science", "Biochemistry"], "article_id"=>452476, "categories"=>["Information And Computing Sciences", "Medicine", "Biochemistry", "Biological Sciences", "Hematology"], "users"=>["Rolf Burghaus", "Katrin Coboeken", "Thomas Gaub", "Lars Kuepfer", "Anke Sensse", "Hans-Ulrich Siegmund", "Wolfgang Weiss", "Wolfgang Mueck", "Joerg Lippert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017626.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Modelling_of_drug_action_/452476", "title"=>"Modelling of drug action.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-22 00:41:16"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

{"start_date"=>"2011-01-01T00:00:00Z", "end_date"=>"2011-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[304, 568, 702, 818, 927, 1027, 1118, 1206, 1285, 1357, 1427, 1500, 1564, 1636, 1705, 1773, 1840, 1909, 1974, 2039, 2106, 2170, 2234, 2296, 2358, 2423, 2484, 2546, 2606, 2673, 2734, 2795, 2857, 2921, 2984, 3046, 3100]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[290, 559, 698, 813, 927, 1028, 1121, 1206, 1289, 1360, 1433, 1501, 1569, 1637, 1707, 1774, 1841, 1911, 1974, 2038, 2103, 2161, 2219, 2280, 2345, 2406, 2466, 2529, 2592, 2654, 2713, 2772, 2835, 2893, 2954, 3020, 3071]}, {"subject_area"=>"/Medicine and health sciences/Anatomy", "average_usage"=>[301, 559, 686, 796, 908, 1013, 1103, 1196, 1281, 1355, 1431, 1507, 1579, 1648, 1711, 1778, 1841, 1910, 1967, 2034, 2087, 2141, 2202, 2261, 2320, 2386, 2444, 2502, 2566, 2632, 2691, 2755, 2812, 2873, 2929, 2997, 3047]}, {"subject_area"=>"/Medicine and health sciences/Hematology", "average_usage"=>[318, 581, 714, 833, 954, 1053, 1145, 1241, 1327, 1405, 1490, 1556, 1632, 1699, 1767, 1834, 1898, 1978, 2041, 2103, 2165, 2225, 2282, 2345, 2403, 2460, 2530, 2582, 2659, 2711, 2768, 2819, 2879, 2939, 2997, 3052, 3100]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[337, 604, 750, 875, 1001, 1107, 1205, 1299, 1391, 1468, 1552, 1629, 1709, 1785, 1862, 1935, 2013, 2081, 2140, 2212, 2281, 2352, 2422, 2489, 2564, 2629, 2698, 2752, 2833, 2880, 2925, 2983, 3042, 3111, 3183, 3250, 3311]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[291, 540, 674, 787, 893, 986, 1087, 1172, 1249, 1319, 1394, 1465, 1526, 1588, 1645, 1713, 1774, 1837, 1903, 1959, 2027, 2085, 2152, 2205, 2259, 2318, 2377, 2436, 2486, 2539, 2603, 2664, 2719, 2779, 2835, 2888, 2944]}]}
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