The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers.
The converting enzyme inhibitor HOE 498 was evaluated in 12 normotensive male volunteers aged 21 to 26. The efficacy of single 5, 10 or 20 mg oral doses in blocking the pressor response to exogenous angiotensin I was tested in 3 of the subjects. All 3 doses of HOE 498 reduced the pressor response to exogenous angiotensin I to below 50% of control within 1,5 h following administration of the drug. Plasma renin and converting enzyme activity, blood angiotensin I, as well as plasma angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of a single dose of 2.5, 5, 10 or 20 mg of HOE 498 to groups of 5 volunteers each. As expected, blood angiotensin I levels and plasma renin activity rose while plasma converting enzyme activity, plasma angiotensin II and aldosterone concentration fell after administration of the drug. While the dose of 2.5 mg did not reduce plasma converting enzyme activity below 20% of control, the higher doses all resulted in plasma converting enzyme inhibition exceeding 90%. No side-effects were observed. It is concluded that in normal volunteers HOE 498 is an effective potent and long-acting converting enzyme inhibitor. Based on these preliminary findings it is expected that 5 mg HOE 948 will turn out to be adequate for therapeutic use.
Bussien
J P
JP
Nussberger
J
J
Porchet
M
M
Waeber
B
B
Brunner
H R
HR
Perisic
M
M
Tansey
M J
MJ
Bomm
M
M
Hajdu
P
P
D000284:Administration, Oral; D000328:Adult; D000803:Angiotensin I / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000097:blood / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D017257:Ramipril; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril