Pharmacokinetic Study in Patients With Chronic Kidney Disease and Healthy Volunteers
Condition: Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to find out how chemicals in the blood of patients with chronic
      kidney disease affect how medications are removed from the body. The patient will take one
      dose of three different drugs, one on each week, for a total of three single doses. The
      investigators want to find out if these three different medications are affected in different
      ways by the chemicals in the blood of patients with kidney disease.
    

Detailed description: 
      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).
    

Intervention name(s): Propranolol; Losartan; Eprosartan
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Propranolol 40mg PO will be given with 6oz of water.Blood samples will be obtained for 12 hours to determine the medication concentration in the plasma. There is no therapeutic effect on this study, since patients will receive a low single dose of the medication, and we'll assess the different pharmacokinetic parameters based on the concentrations of the medicine in plasma.; Losartan 50mg PO will be given with 6oz of water. Blood samples will be obtained for 12 hours to determine the medication concentration in the plasma. There is no therapeutic effect on this study, since patients will receive a low single dose of the medication, and we'll assess the different pharmacokinetic parameters based on the concentrations of the medicine in plasma.; Erythromycin 125mg PO will be given with 6oz of water. Blood samples will be obtained for 12 hours to determine the medication concentration in the plasma. There is no therapeutic effect on this study, since patients will receive a low single dose of the medication, and we'll assess the different pharmacokinetic parameters based on the concentrations of the medicine in plasma.
Other intervention name(s): Propranolol Hydrochloride; Ciplar; Ciplar LA; Inderal; Inderal LA; Avlocardyl; Deralin; Dociton; Inderalici; InnoPran XL; Sumial; Anaprilinum; Bedranol SR; Cozaar; Losartan potassium; Anin; Teveten; Eprozar; Teveten HCT (paired with hydrochlorothiazide); Teveten Plus (paired with hydrochlorothiazide)
Intervention MeSH terms: Losartan; Propranolol; Hydrochlorothiazide; Eprosartan
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)