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Zhou2015 - Blood coagulation model predicting effects of factor Xa inhibitors

ABSTRACT: Blood coagulation model investigating effects of Xa-inhibitors (Rivaroxaban and Apixaban). Model is an extension of Pohl1994 and reduced from Wajima2009.Encoding the model from the supplementary files results in 43 species, 82 reactions and 111 parameters. Including the drug (Xa-inhibitor) and drug-Xa complexes results in 46 species, 84 reactions and 115 parameters (+1 dummy variable to change inhibitory kinetic parameters depending on which drug is simulated). The publication lists there being 45 species, 84 reactions and 116 parameters. Publication figure 2 has 45 species present however the complex VIIa:Xa (reaction 51 involving Xa and VIIa) is not shown. This figure also has numerous small errors such as listing IXa:ATIII complex twice (instead of one being XIa:ATIII), not showing XIa:ATIII, typo ('Va' -> Va), typo (IXa + VIIIa -> IXA:'VIIa'). Rate laws for Xa-drug interactions were assumed to be mass action.

SUBMITTER: Matthew Roberts 

PROVIDER: MODEL1806070001 | biostudies-other |

SECONDARY ACCESSION(S): 26783501

REPOSITORIES: biostudies-other

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A Systems Pharmacology Model for Predicting Effects of Factor Xa Inhibitors in Healthy Subjects: Assessment of Pharmacokinetics and Binding Kinetics.

Zhou X X   Huntjens Drh D   Gilissen Rahj R  

CPT: pharmacometrics & systems pharmacology 20151009 11

Factor Xa (FXa) emerged as a promising target for effective anticoagulation and several FXa inhibitors are now available for the prevention of venous thromboembolism. However, in previously reported pharmacokinetic/pharmacodynamic (PK/PD) models, the complex coagulation processes and detailed information of drug action are usually unclear, which makes it difficult to predict clinical outcome at the drug discovery stage. In this study, a large-scale systems pharmacology model was developed based  ...[more]

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