Modeling the pharmacodynamics of rHuEPO, a blood doping drug

Abstract

For this study, a model to analyze the dynamic e ects of recombinant human erythropoietin (rHuEPO), a very popular and hard to detect blood doping drug, is constructed. rHuEPO is the synthetic version of erythropoietin (EPO) hormone which is responsible for the red blood cell production depending on the blood oxygen levels in the body. The usage of rHuEPO in competitions is prohibited by World Anti-Doping Agency (WADA). The personalized tests aiming to detect the usage of rHuEPO are mainly carried out by screening the various blood values that are a ected by rHuEPO, which are the hematocrit (red blood cell count), hemoglobin concentration and reticulocyte count. Accordingly, red blood cell regulation structure and the pathways of rHuEPO in the body and their e ects on red blood cells are included into the model. Various validation scenarios are conducted to show that the model is consistent with the relevant literature and data. Next, the model is run under two di erent disequilibrium conditions to reveal the base dynamic behaviors of the model. Our aim is to discuss the dynamic patterns for rHuEPO users and how these patterns di er for rHuEPO users and altitude trainers (a legitimate practice for enhancing blood oxygen capacity). Moreover, we want to analyze the masking of rHuEPO usage with altitude training. Thus, three scenarios are investigated: (1) sensitivity analysis with rHuEPO usage; (2) altitude training; (3) altitude training together with rHuEPO usage. According to the simulation results of our scenarios, various blood values have distinct dynamic behaviors in three distinct periods: before the competition during drug use, during the competition when drug provides competitive advantage, and after the competition. We conclude that these ndings can provide a basis to design strong anti-doping tests. Our model can be personalized for individual athletes and hard-to-cheat personalized tests can be developed against rHuEPO use.