Clinical Use of Rivaroxaban: Pharmacokinetic and Pharmacodynamic Rationale for Dosing Regimens in Different Indications

Target-specific oral anticoagulants have become increasingly available as alternatives to traditional agents for the management of a number of thromboembolic disorders. To date, the direct Factor Xa inhibitor rivaroxaban is the most widely approved of the new agents. The dosing of rivaroxaban varies and adheres to specific schedules in each of the clinical settings in which it has been investigated. These regimens were devised based on the results of phase II dose-finding studies and/or pharmacokinetic modeling, and were demonstrated to be successful in randomized, phase III studies. In most cases, the pharmacodynamic profile of rivaroxaban permits once-daily dosing. A once-daily dose is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery, the long-term prevention of stroke in patients with non-valvular atrial fibrillation, and the long-term secondary prevention of recurrent VTE. Twice-daily dosing is required in the acute phase of treatment in patients with VTE and in the combination of rivaroxaban with standard single or dual antiplatelet therapy for secondary prevention after acute coronary syndrome events. This article reviews the empirical and clinical rationale supporting the dose regimens of rivaroxaban in each clinical setting

MRI and CT in the diagnosis of coronary artery disease: indications and applications

In recent years, technical advances and improvements in cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI) have provoked increasing interest in the potential clinical role of these techniques in the non-invasive work-up of patients with suspected coronary artery disease (CAD) and correct patient selection for these emerging imaging techniques. In the primary detection or exclusion of significant CAD, e.g. in the patient with unspecific thoracic complaints, and also in patients with known CAD or advanced stages of CAD, both CT and MRI yield specific advantages. In this review, the major aspects of non-invasive MR and CT imaging in the diagnosis of CAD will be discussed. The first part describes the clinical value of contrast-enhanced non-invasive CT coronary angiography (CTCA), including the diagnostic accuracy of CTCA for the exclusion or detection of significant CAD with coronary artery stenoses that may require angioplastic intervention, as well as potentially valuable information on the coronary artery vessel wall. In the second section, the potential of CT for the imaging of myocardial viability and perfusion will be highlighted. In the third and final part, the range of applications of cardiac MRI in CAD patients will be outlined

Effects of macromolecular crowding on intracellular diffusion from a single particle perspective

Compared to biochemical reactions taking place in relatively well-defined aqueous solutions in vitro, the corresponding reactions happening in vivo occur in extremely complex environments containing only 60–70% water by volume, with the remainder consisting of an undefined array of bio-molecules. In a biological setting, such extremely complex and volume-occupied solution environments are termed ‘crowded’. Through a range of intermolecular forces and pseudo-forces, this complex background environment may cause biochemical reactions to behave differently to their in vitro counterparts. In this review, we seek to highlight how the complex background environment of the cell can affect the diffusion of substances within it. Engaging the subject from the perspective of a single particle’s motion, we place the focus of our review on two areas: (1) experimental procedures for conducting single particle tracking experiments within cells along with methods for extracting information from these experiments; (2) theoretical factors affecting the translational diffusion of single molecules within crowded two-dimensional membrane and three-dimensional solution environments. We conclude by discussing a number of recent publications relating to intracellular diffusion in light of the reviewed material