MOEXIPRIL, A NEW ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITOR - PHARMACOLOGICAL CHARACTERIZATION AND COMPARISON WITH ENALAPRIL

The pharmacodynamic profile of the new angiotensin-converting enzyme ( ACE) inhibitor moexipril and its active diacid, moexiprilat, was studi ed in vitro and in vivo. In vitro, moexiprilat exhibited a higher inhi bitory potency than enalaprilat against both plasma ACE and purified A CE from rabbit lung. Upon oral administration of moexipril (10 mg/kg/d ay) to spontaneously hypertensive rats, plasma angiotensin II concentr ation decreased to undetectable levels, plasma AGE activity was inhibi ted by 98% and plasma angiotensin I concentration increased 8.6-fold 1 h after dosing. At 24 h, plasma angiotensin I and angiotensin II conc entrations had returned to pretreatment levels, whereas plasma ACE act ivity was still inhibited by 56%. Four-week oral administration of moe xipril (0.1-30 mg/kg/day) to spontaneously hypertensive rats lowered b lood pressure and differentially inhibited ACE activity in plasma, lun g, aorta, heart and kidney in a dose-dependent fashion. Equidose treat ment (10 mg/kg/day) with moexipril and enalapril over 4 weeks led to c omparable decreases in blood pressure, inhibition of plasma ACE and re duction of plasma angiotensinogen and to a similar attenuation of the presser responses to angiotensin I and potentiation of the depressor r esponses to bradykinin. In contrast, ACE inhibition in aorta, heart an d lung was significantly greater with moexipril than with enalapril, w hereas in the kidney both drugs inhibited ACE activity to a similar ex tent. In summary, moexipril is an orally active ACE inhibitor that is comparable to enalapril in potency and duration of antihypertensive ac tivity. The results of the present study demonstrate that 1) the antih ypertensive potency of a given ACE inhibitor cannot be predicted from its in vitro characteristics and 2) the degree of blood pressure reduc tion does not correlate with tissue ACE inhibition.