Key Points
- To evaluate the pharmacological properties, vascular ACE binding, potency, and excretion characteristics of the novel prodrug ACE inhibitor CS-622 relative to enalapril and captopril.
- Assessed ACE inhibitory potency of CS-622 diacid against enalaprilat in isolated rabbit lung preparations and isolated rat aortic strips, including persistence of inhibition after washout.
- Compared the onset, magnitude, and duration of action between oral CS-622 versus enalapril and intravenous CS-622 diacid versus enalaprilat.
- Evaluated the impact of eliminated renal excretory function on the pharmacodynamics of CS-622 compared to captopril.
- CS-622 diacid demonstrated 3 times the inhibitory potency of enalaprilat on isolated rat aorta and washed out significantly more slowly, demonstrating tighter binding to vascular ACE.
- Oral administration of CS-622 was 3 times more potent than enalapril with a faster onset of action, while intravenous CS-622 diacid had a longer duration of action than enalaprilat.
- Elimination of renal excretory function potentiated the action of captopril but did not potentiate CS-622, indicating that only a minor fraction of CS-622 is excreted via the kidneys.
Structured PICO
PPopulationPreclinical models including isolated rabbit lung ACE, isolated rat aorta, and in vivo animal models
IInterventionCS-622 (prodrug) and CS-622 diacid (active form)
CComparatorEnalapril, enalaprilat, and captopril
OOutcomeACE inhibitory potency and duration of actionsurrogate
CS-622 is a novel ACE inhibitor that demonstrates greater potency, faster onset, longer duration of action, and less reliance on renal excretion compared to enalapril and captopril in preclinical models.