Pharmacokinetic Study in Patients With Chronic Kidney Disease and Healthy Volunteers

It has been demonstrated that proteins known as drug transporters in different human organs and tissues are important for a drug to be absorbed, distributed, metabolized, and eliminated (ADME)18. The chemical properties of drugs can affect whether it needs a transporter protein to enter the cell or not. It is not well known how these proteins are affected in chronic disease and how different drugs may be absorbed, metabolized, or eliminated differently in certain diseases. Preliminary studies suggest that some drugs (those requiring drug transporter proteins) may show altered elimination in the presence of uremic toxins. Uremic toxins are substances accumulated in the blood of patients with chronic kidney disease and many are not removed through hemodialysis (HD). We hypothesize that the different classes of drugs (BDDCS class1, 2, and 3) will have different degrees of changes in AUC, meaning that for a class 1 drug we would see less of a change in AUC than in a class 3 drug because a class 3 drug requires transporters. Previous studies can't make that comparison because they used different patients for each drug, so even if there were a change in a class 1 drug, it can't be compared to a class 3 drug. In order to get an accurate comparison, we will test the three drugs on the same patient and see how he AUC changes from drug to drug within the same patient comparing it to the healthy volunteer (taking the same three drugs).