ENALAPRIL AND CARVEDILOL WITH INHIBITION OF TRANSPORTERS BY FAMOTIDINE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Purpose: This clinical study will evaluate the effect of famotidine on the plasma concentrations and renal clearance of enalapril and carvedilol, two drugs used in the treatment of chronic heart failure (HF). Participants: Patients with stable chronic HF (New York Heart Association (NYHA) class III), who currently are taking enalapril and carvedilol as part of their HF treatment will be recruited to participate in this study. Procedures (methods): This will be an open-labeled, randomized, crossover study in male and female adult volunteers of any ethnicity with HF. Blood and urine samples will be collected for 12 hours and analyzed for enalapril/enalaprilat and carvedilol (R and S enantiomers) without famotidine administration (control) and after administration of 20 mg famotidine twice daily for three days. Changes in pharmacokinetic parameters, particularly area under the concentration versus time curve (AUC) and renal clearance (CLR), will be evaluated.