First dose response and 24-hour antihypertensive efficacy of the new once-daily angiotensin converting enzyme inhibitor, ramipril.
The reduction in blood pressure (BP) after the first dose and after 8 weeks of treatment with a new once-daily angiotensin converting enzyme (ACE) inhibitor, ramipril, was examined in 12 untreated hypertensive patients, using ambulatory intraarterial BP monitoring. The first period of monitoring began 24 hours before the first dose was given, and continued for 24 hours afterwards. A second 24-hour period of monitoring was carried out after 8 weeks of treatment, commencing immediately after the morning dose. Angiotensin II levels and serum drug levels were measured at 0, 2, 6 and 24 hours after the acute dose. BP decreased progressively from the first hour after the first dose, reached a maximum in the fifth hour (p less than 0.001) and then the effect diminished. The maximum reduction of systolic BP in any patient was 64 mm Hg, the minimum 4 mm Hg. Blood pressure was significantly (p less than 0.05) reduced throughout the 24 hours after dosing, with a mean daytime reduction of 13/12 mm Hg, and a mean nighttime reduction of 15/7 mm Hg. Angiotensin II levels were significantly (p less than 0.02) and maximally reduced by 2 hours after administration, but the reduction was no longer significant after 24 hours. Serum drug levels were also maximal 2 hours after administration. The trial population could be clearly divided into groups of good and poor responders on the basis of BP reduction. The angiotensin II levels were higher before treatment, and decreased further, in all patients with a good response than in those with a poor response.(ABSTRACT TRUNCATED AT 250 WORDS)
Heber
M E
ME
Department of Cardiology, Northwick Park Hospital, Harrow, Middlesex, England.
Brigden
G S
GS
Caruana
M P
MP
Lahiri
A
A
Raftery
E B
EB
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination / Q000379:methods; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D017257:Ramipril; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D000804:Angiotensin II; D017257:Ramipril