Comparison of the acute and chronic antihypertensive effect of two once-daily doses of spirapril by invasive twenty-four-hour ambulatory blood pressure monitoring.
Spirapril is a new non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which is eliminated mainly through the liver. In a placebo-controlled study the acute and chronic (2 weeks) antihypertensive effects of two doses of spirapril (12.5 and 25 mg) were assessed by invasive 24-h ambulatory blood pressure monitoring in two groups of eight hypertensive subjects. After the first doses of 12.5 and 25 mg, blood pressure rapidly decreased, with a nadir after 4-6 h. At this time, mean arterial pressure was decreased by 24 +/- 2% with the 12.5 and 19 +/- 1% with the 25-mg dose. The antihypertensive response was sustained for almost the whole 24-h period with the 25-mg dose, but it was attenuated during the second half of the 24-h blood pressure monitoring with the 12.5-mg dose, leaving a residual antihypertensive effect of 6 +/- 2% 24 h after dosing. Compared with the response to the first dose, the antihypertensive response after 2 weeks of treatment was similar to that following the 12.5-mg dose, but with the 25-mg dose the response during the second half of the 24-h monitoring period, especially during the night, was attenuated. The reason for this attenuated antihypertensive response during prolonged ACE inhibition remains to be established.
van den Meiracker
A H
AH
Department of Internal Medicine I, University Hospital, Dijkzigt, Rotterdam, The Netherlands.
Man in 't Veld
A J
AJ
Ritsema van Eck
H J
HJ
Schalekamp
M A
MA
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015924:Blood Pressure Monitors; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004656:Enalapril / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; C052555:spirapril