B. Beermann et al., ACUTE HEMODYNAMIC-EFFECTS AND PHARMACOKINETICS OF RAMIPRIL IN PATIENTS WITH HEART-FAILURE - A PLACEBO-CONTROLLED 3-DOSE STUDY, European Journal of Clinical Pharmacology, 45(3), 1993, pp. 241-246
The aim of the present study was primarily to evaluate the haemodynami
c effects of the ACE-inhibitor ramipril which is active via its metabo
lite ramiprilat. Ramipril 1.25,2.5 and 5 mg and placebo was administer
ed orally to 4 groups of 12 patients with heart failure (NYHA III) in
a double-blind randomised, parallel study. Haemodynamics were monitore
d for 24 h and blood was sampled and urine collected for up to 96 h. I
n the placebo-treated group the cardiac index (CI) was significantly i
ncreased (15.8%) and right atrial pressure decreased (26.6%). Ramipril
1.25 mg had insignificant haemodynamic effects compared to placebo an
d the 2.5 mg dose had significant effects on some haemodynamic variabl
es. Ramipril 5 mg had pronounced and sustained effects on pulmonary ar
tery pressure, which fell by 43.7 %, and pulmonary capillary wedge pre
ssure (PCWP; -59.1 %); systemic vascular resistance was also decreased
21 %. A significant effect on CI was only seen after 2.5 mg ramipril
(+ 7.4 %).The mean maximal degree of ACE inhibition was 73.2, 90.4 and
98.5 %, respectively, after the three doses of ramipril. Complete inh
ibition of ACE-activity was seen at a mean plasma concentration of ram
iprilat of 4.7 ng . ml-1. The degree of inhibition declined with a hal
f life of about 75 h. There was a significant relation between the deg
ree of ACE-inhibition and change in PCWP but not with the change in SV
R. Ramipril was mainly eliminated in the form of ramiprilat and inacti
ve metabolites.