Pharmacodynamic effects of a single 10-mg dose of the angiotensin converting enzyme inhibitor ramipril in patients with impaired renal function.
A single oral 10-mg dose of ramipril, a long-acting angiotensin converting enzyme (ACE) inhibitor, was given to 24 hypertensive patients with different degrees of renal function. Creatinine clearance ranged from below 15 ml/min (n = 9) to above 80 ml/min (n = 3). Serial blood samples were taken for the determination of ACE activity, plasma renin activity (PRA), aldosterone (ALDO), angiotensin II (AT II), and serum creatinine (CR). Blood pressure was also monitored before and after medication. After administration of ramipril systolic and diastolic blood pressure (BP) fell; the decreases were unrelated to renal function. Peak BP-lowering effect was seen at 6 h basal, 174 +/- 19.5/102.6 +/- 8.9 to 149.8 +/- 19.7/87.6 +/- 13.3 mm Hg (mean +/- SD; p less than 0.001). ACE inhibition occurred within 2 h, being maximal at 4 h: basal, 82.6 +/- 17.9 to 0.2 +/- 0.6 nmol/ml/min (p less than 0.001). The greater the renal impairment, the longer the ACE inhibition. Angiotensin II was reduced maximally at 10 h after dosing, from 10.4 +/- 5.4 to 6.2 +/- 3.6 pg/ml (p less than 0.01). Aldosterone also fell from 212 +/- 188.4 to 134 +/- 73.3 pg/ml at 6 h (p less than 0.01). Plasma creatinine was unchanged: 401.3 +/- 315.7 to 394.9 +/- 306.1 nmol/L (NS). Ramipril, given as a single oral dose, lowers BP in hypertensives with both normal and impaired renal function, inhibits ACE activity, and causes no change in serum creatinine.
Ocón-Pujadas
J
J
Hypertension Unit, Fundación Puigvert, Barcelona, Spain.
Debusmann
E R
ER
Jane
F
F
Lahn
W
W
Irmisch
R
R
Mora
J
J
Grötsch
H
H
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017257:Ramipril; D012083:Renin / Q000097:blood; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D000804:Angiotensin II; D000450:Aldosterone; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D017257:Ramipril