Pharmacokinetic Study in Patients With Chronic Kidney Disease and Healthy Volunteers

NCT01087749 | Completed Phase 1 DMC

• 1 other identifier: PKUCSF2010
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic parameters

  Three 12-hour days visits (on different weeks) will be investigated to obtain blood samples for 12 hours for three different medications. Blood samples will be obtained 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.

  3 weeks

Study Arms (2)

Chronic Kidney Disease

EXPERIMENTAL

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.

Drug: Propranolol; Drug: Losartan; Drug: Eprosartan

Healthy Volunteers

EXPERIMENTAL

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

Drug: Propranolol; Drug: Losartan; Drug: Eprosartan

Interventions

Propranolol 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.

Also known as: Propranolol Hydrochloride, Ciplar, Ciplar LA, Inderal, Inderal LA, Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Sumial, Anaprilinum, Bedranol SR

Chronic Kidney Disease; Healthy Volunteers

Losartan 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.

Also known as: Cozaar, Losartan potassium, Anin

Chronic Kidney Disease; Healthy Volunteers

Eprosartan 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.

Also known as: Teveten, Eprozar, Teveten HCT (paired with hydrochlorothiazide), Teveten Plus (paired with hydrochlorothiazide)

Chronic Kidney Disease; Healthy Volunteers

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

Clinical Reserach Center, UCSF

San Francisco, California, 94143, United States

Location

Related Publications (13)

• Bianchetti G, Graziani G, Brancaccio D, Morganti A, Leonetti G, Manfrin M, Sega R, Gomeni R, Ponticelli C, Morselli PL. Pharmacokinetics and effects of propranolol in terminal uraemic patients and in patients undergoing regular dialysis treatment. Clin Pharmacokinet. 1976;1(5):373-84. doi: 10.2165/00003088-197601050-00004.

  PMID: 1017154 BACKGROUND

• Lam JL, Shugarts SB, Okochi H, Benet LZ. Elucidating the effect of final-day dosing of rifampin in induction studies on hepatic drug disposition and metabolism. J Pharmacol Exp Ther. 2006 Nov;319(2):864-70. doi: 10.1124/jpet.106.108282. Epub 2006 Aug 11.

  PMID: 16905688 BACKGROUND

• Lau YY, Okochi H, Huang Y, Benet LZ. Pharmacokinetics of atorvastatin and its hydroxy metabolites in rats and the effects of concomitant rifampicin single doses: relevance of first-pass effect from hepatic uptake transporters, and intestinal and hepatic metabolism. Drug Metab Dispos. 2006 Jul;34(7):1175-81. doi: 10.1124/dmd.105.009076. Epub 2006 Apr 19.

  PMID: 16624870 BACKGROUND

• Lau YY, Huang Y, Frassetto L, Benet LZ. effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. Clin Pharmacol Ther. 2007 Feb;81(2):194-204. doi: 10.1038/sj.clpt.6100038. Epub 2006 Dec 27.

  PMID: 17192770 BACKGROUND

• Guevin C, Michaud J, Naud J, Leblond FA, Pichette V. Down-regulation of hepatic cytochrome p450 in chronic renal failure: role of uremic mediators. Br J Pharmacol. 2002 Dec;137(7):1039-46. doi: 10.1038/sj.bjp.0704951.

  PMID: 12429576 BACKGROUND

• Martin DE, Chapelsky MC, Ilson B, Tenero D, Boike SC, Zariffa N, Jorkasky DK. Pharmacokinetics and protein binding of eprosartan in healthy volunteers and in patients with varying degrees of renal impairment. J Clin Pharmacol. 1998 Feb;38(2):129-37. doi: 10.1002/j.1552-4604.1998.tb04401.x.

  PMID: 9549643 BACKGROUND

• Michaud J, Naud J, Chouinard J, Desy F, Leblond FA, Desbiens K, Bonnardeaux A, Pichette V. Role of parathyroid hormone in the downregulation of liver cytochrome P450 in chronic renal failure. J Am Soc Nephrol. 2006 Nov;17(11):3041-8. doi: 10.1681/ASN.2006010035. Epub 2006 Oct 4.

  PMID: 17021269 BACKGROUND

• Naud J, Michaud J, Leblond FA, Lefrancois S, Bonnardeaux A, Pichette V. Effects of chronic renal failure on liver drug transporters. Drug Metab Dispos. 2008 Jan;36(1):124-8. doi: 10.1124/dmd.107.018192. Epub 2007 Oct 16.

  PMID: 17940133 BACKGROUND

• Nolin TD, Naud J, Leblond FA, Pichette V. Emerging evidence of the impact of kidney disease on drug metabolism and transport. Clin Pharmacol Ther. 2008 Jun;83(6):898-903. doi: 10.1038/clpt.2008.59. Epub 2008 Apr 2.

  PMID: 18388866 BACKGROUND

• Sica DA, Halstenson CE, Gehr TW, Keane WF. Pharmacokinetics and blood pressure response of losartan in end-stage renal disease. Clin Pharmacokinet. 2000 Jun;38(6):519-26. doi: 10.2165/00003088-200038060-00005.

  PMID: 10885588 BACKGROUND

• Sun H, Huang Y, Frassetto L, Benet LZ. Effects of uremic toxins on hepatic uptake and metabolism of erythromycin. Drug Metab Dispos. 2004 Nov;32(11):1239-46. doi: 10.1124/dmd.104.000521. Epub 2004 Jul 30.

  PMID: 15286055 BACKGROUND

• 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.

  PMID: 12675874 BACKGROUND

• Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005 Jan;22(1):11-23. doi: 10.1007/s11095-004-9004-4.

  PMID: 15771225 BACKGROUND

MeSH Terms

Conditions

Kidney Diseases

Interventions

Propranolol; propranolol CR; Losartan; eprosartan; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Leslie Z Benet, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Lynda Frassetto, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2010
• First Posted: March 16, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 30, 2013

Record last verified: 2013-05

Locations

US (1)