The primary objective is the characterization of the RAS peptide profiles after single and repeated oral administration of a renin inhibitor, an ACE inhibitor and an angiotensin receptor blocker in healthy volunteers. Secondary objectives are the correlation of RAS peptide profiles with pharmacokinetic profiles of the different RAS inhibitors and with pharmacodynamic parameters such as blood pressure and heart rate. Output of the classic RAS system will be assessed using aldosterone concentrations. Fluid and sodium intake will be monitored using sodium concentration and total volume in 24h urine.
The results of a pilot study have shown that single doses of different RAS inhibitors produce characteristic changes of the RAS peptide profiles. In a first step this finding needs to be verified in a larger number of healthy subjects. Since it is unknown, whether the changes that were observed within hours after a single inhibitor dose are stable over time, the profiles also need to be investigated under steady-state conditions of the different inhibitors. Comparison of RAS peptide profiles after single dose and under steady-state conditions will also allow to detect whether the peptide profiles are altered by compensatory mechanisms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
12
Department Clinical Pharmacology, University Hospital Basel
Basel, Switzerland
RAS-peptide profile
Time frame: 0-192h
Blood pressure and heart rate
Time frame: 0-192 h
Aldosterone concentrations
Time frame: 0-192 h
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