Presenter: Steven McGreal, Ph.D, Study Director at SEKISUI XenoTech Abstract: Pharmacokinetic (PK) parameters of a new drug candidate are typically determined by measuring the drug’s concentration in plasma. However, many drugs have the potential to bind to or diffuse into red blood cells (RBCs), and because RBCs comprise at least 99% of cellular space in blood, this binding potential could significantly impact drug clearance and cause inaccuracies in PK calculations. Usually, pharmacokinetic parameters are determined by measuring drug concentration in plasma at successive time points, as opposed to measuring the drug concentration in whole blood. However, failing to take into account the potential for a drug to sequester into red blood cells may lead to a misinterpretation of pharmacokinetic data and provide an overestimation of drug’s clearance. For example, certain compounds such as chloroquine are sequestered into red blood cells, thereby causing them to have a blood to plasma ratio that is greater than 1. This illustrates the importance of accounting for the amount of drug potentially sequestered into red blood cells, in addition to the extent of plasma protein binding, when trying to determine the true amount of free unbound drug available in the plasma (fu_plasma). The assay is designed to determine the blood to plasma ratio of your drug at three concentrations, provide red blood cell distribution percentage, and measure stability. Between our SEKISUI partner laboratory in Japan and headquarters in Kansas City, we can work with whole blood from human donors and preclinical animal species including rat, mouse, dog, monkey, rabbit, and miniature pig.