| Population Pharmacokinetics and Pharmacodynamics of Rivaroxaban in Patients with Acute Coronary Syndromes. | |
| | |
MedLine Citation:
|
PMID: 22242932 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Aims: The aim of this analysis was to use a population approach to facilitate the understanding of the pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndrome (ACS) and to evaluate the influence of patient covariates on the exposure of rivaroxaban in patients with ACS. Methods: A population pharmacokinetic model was developed using pharmacokinetic samples from 2290 patients in ATLAS ACS-TIMI 46. The relationship between pharmacokinetics and the primary pharmacodynamic endpoint, prothrombin time (PT) was evaluated. Results: The pharmacokinetics of rivaroxaban in patients with ACS was adequately described by an oral one-compartment model. The estimated absorption rate, apparent clearance and volume of distribution were 1.24 h(-1 ) (interindividual variability: 139%), 6.48 L/h (31%), and 57.9 L (10%), respectively. Simulations indicate that the influences of renal function, age, and body weight on exposure in ACS patients are consistent with the findings in previous Phase 1 studies. Rivaroxaban plasma concentrations exhibit a close-to-linear relationship with PT in the ACS population with little interindividual variability. The estimated pharmacokinetic/pharmacodynamic parameters for the ACS patients were comparable to those for venous thromboembolism prevention, deep vein thrombosis, and atrial fibrillation patients. Conclusions: The similarity in pharmacokinetics/pharmacodynamics of rivaroxaban among different patient populations and the low interindividual variability in exposure-PT relationship indicate the anticoagulant effect of rivaroxaban is highly predictable and consistent across all the patient populations studied. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society. |
| | |
Authors:
|
X S Xu; K Moore; P Burton; K Stuyckens; W Mueck; S Rossenu; A Plotnikov; M Gibson; A Vermeulen |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-13 |
Journal Detail:
|
Title: British journal of clinical pharmacology Volume: - ISSN: 1365-2125 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
|
Clinical Pharmacology, Advanced PK-PD Modeling and Simulation, Janssen Research & Development, Titusville, NJ, USA Clinical Pharmacology, Janssen Research & Development, Titusville, NJ, USA Janssen Research & Development, Raritan, NJ, USA Clinical Pharmacology, Advanced PK-PD Modeling and Simulation, Janssen Research & Development, Beerse, Belgium Bayer Pharma AG, Wuppertal, Germany Cardiovascular Division, Beth Israel Hospital, Harvard Medical School, Boston, MA, USA Current affiliation: Ablynx nv, Zwijnaarde, Belgium. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Comparisons between in vitro whole cell imaging and in vivo zebrafish-based approaches for identifyi...
Next Document: Development of the Surface-SFED Models for Polar Solvents.