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Pharmacometric approaches to optimize use of drugs and dialysis treatments in patients with chronic kidney disease
Published on December 4, 2014 30 min
Other Talks in the Series: The Kidney in Health and Disease
Proteomics in kidney disease: clinical considerations
- Prof. Peter Rossing
- Steno Diabetes Center, Denmark
This is a talk for the Henry Stewart Collection. I'm Marc Pfister, a trained nephrologist. I worked in Switzerland and in the US, in California at UCSF, before I joined a couple of pharmaceutical companies. And now I work as Chief Medical Officer for a global consulting company. The topic of this lecture is "Pharmacometric Approaches to Optimize Use of Drugs and Dialysis Treatments in Patients with Chronic Kidney Disease."
Before we go to a couple of case studies, I want to briefly review the concept of therapeutic window. The goal of every treatment in our patients is to improve, extend, save lives. So the goal is to optimize the dosing so that patients have maximum benefit and minimal risk for adverse events, safety events. To obtain that goal, we need to understand the exposure range, the concentration range for a given drug and treatment. And the goal is to have a maturity of patients with this exposure range so that, again, we can optimize benefits and minimize the risk for adverse events for these patients. And that range of target concentrations is called therapeutic window.
This is an example from the cardiovascular space. This plot shows a blue line and a red line. It compares a new class of drugs to prevent thromboembolic events, Factor Xa inhibitors, and compares this new class with a standard of care, which is Enoxaparin, which is shown as a black horizontal line. The goal is to optimize dosing for this new class of drug so that the blue and the red line are below the black line. The blue line represents thromboembolic events. So the lower the number, the better. That means more thromboembolic events were protected. The red line is increasing with dose. That is, the safety curve. The higher dose, the more bleeding events. The same goal here is to have this red line at the low level. We can see that there is a window in the middle where both the blue and the red line are below the black line. So that means for this class of drug, there is a dose range that is associated with better efficacy. The blue line is below the black line. And also, better safety. And that is the therapeutic window for this class of drug. And this plot is based on data from a hundred different trials. So the goal is with pharmacometric approaches to integrate data from different trials and to quantify this therapeutic window so that we can compare different compounds and different doses and optimize treatment for patients.