The overall goal of this project is to assess and probe potential mechanisms of the decreased response to furosemide that occurs in a variety of clinical settings such as congestive heart failure, liver disease, and renal disease. Resistance to diuretics could occur through disease-induced changes in disposition of the drug including altered quantity or time course of absorption after oral administration or changed disposition after intravenous administration. Alternatively, or in addition, disease-induced changes in response to amounts of drug delivered to the site of action could occur. We propose to assess in patients with diseases in which resistance to diuretics occurs whether changes in pharmacokinetics and/or in pharmacodynamics occur. If so, we propose to attempt correlations of changes in kinetics with indices of disease severity to allow speculation as to possible mechanisms of altered handling and to allow predictions in other patients which might facilitate therapeutic strategy. We also propose studies to attempt to elucidate possible mechanisms of altered pharmacodynamics which, in turn, may provide insights into the pathogenesis of solute retention in these disease states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Modified Research Career Development Award (K04)
Project #
5K04DK001733-04
Application #
3072486
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1986-03-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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Carlstedt, B C; Uaamnuichai, M; Day, R B et al. (1989) Aminoglycoside dosing in pediatric patients. Ther Drug Monit 11:38-43
Voelker, J R; Jameson, D M; Brater, D C (1989) In vitro evidence that urine composition affects the fraction of active furosemide in the nephrotic syndrome. J Pharmacol Exp Ther 250:772-8