Pharmacokinetic Study in Patients With Chronic Kidney Disease and Healthy Volunteers

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.

Timeline

Start

2010-03

Primary completion

2012-12

Completion

2012-12

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications