Pharmacokinetic Study in Patients With Chronic Kidney Disease and Healthy Volunteers

NCT ID: NCT01087749

Last Updated: 2013-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2012-12-31

Brief 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).

Conditions

Kidney Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

Chronic Kidney Disease

Propranolol, Losartan, and Eprosartan will be administered to patients who have been diagnosed with Chronic Kidney disease and have a glomerular filtration rate (GFR) below 40ml/min.

Group Type: EXPERIMENTAL

Propranolol

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Eprosartan

Intervention Type: DRUG

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.

Healthy Volunteers

Propranolol, Losartan, and Eprosartan will be administered to healthy volunteers without chronic kidney disease.

Group Type: EXPERIMENTAL

Propranolol

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Eprosartan

Intervention Type: DRUG

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.

Interventions

Propranolol

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.

Intervention Type: DRUG

Losartan

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.

Intervention Type: DRUG

Eprosartan

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.

Intervention Type: DRUG

Other Intervention Names

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)

Eligibility Criteria

Inclusion Criteria

• Male or Female 18-70 years of age.
• Healthy volunteers or chronic kidney disease (GFR<40)
• Be able to provide written informed consent and comply with requirements of the study.
• Avoid eating grapefruit and drinking grapefruit juice from 7 days prior to the first study day until completion of the study.
• Abstinence from alcoholic beverages, caffeinated beverages and orange juice from 6pm the night before a study day until completion of the study day.
• Fast from food and beverages at least 8 hours prior to medication dosing.
• Be able to read, speak, and understand English.

Exclusion Criteria

• Subjects with contraindications to taking the study drugs
• Subjects with known allergies to propranolol, losartan, or eprosartan.
• Subjects who smoke tobacco.
• Subjects with ongoing alcohol or illegal drug use.
• Subjects who are pregnant, lactating, or attempting to conceive.
• Subjects unable to maintain adequate birth control during the study.
• Subjects unable to follow protocol instructions or protocol criteria.
• Subjects with hematocrit < 30mg/dL.
• Subjects who are insulin requiring diabetics.
• Subjects with low, or low normal blood pressure (systolic blood pressure [BP] <100mmHg)
• Subjects with uncontrolled high blood pressure.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leslie Z Benet, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Lynda Frassetto, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Clinical Reserach Center, UCSF

San Francisco, California, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R, Descamps-Latscha B, Henle T, Jorres A, Lemke HD, Massy ZA, Passlick-Deetjen J, Rodriguez M, Stegmayr B, Stenvinkel P, Tetta C, Wanner C, Zidek W; European Uremic Toxin Work Group (EUTox). Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003 May;63(5):1934-43. doi: 10.1046/j.1523-1755.2003.00924.x.

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Other Identifiers

PKUCSF2010

Identifier Type: -

Identifier Source: org_study_id