Enalapril maleate and a lysine analogue (MK‐521) in normal volunteers; relationship between plasma drug levels and the renin angiotensin system.

1 Two single doses of 10 mg each of the converting enzyme inhibitor enalapril maleate or MK‐421 and of its lysine analogue (MK‐521) were administered p.o. to twelve male volunteers. 2 The active diacid metabolite of MK‐421 and the lysine analogue were determined by radioimmunoassay and MK‐421 by the active metabolite method following in vitro hydrolysis. 3 Peak serum levels of MK‐421, active metabolite and lysine analogue were reached within 1, 3 to 4, and 6 h respectively. Practically all MK‐421 had disappeared from serum within 4 h. 4 A close correlation between percent inhibition of plasma converting enzyme activity and the serum concentration of active metabolite was observed (r = 0.98, n = 171, P less than 0.001). Similarly, converting enzyme blockade as expressed by the ratio plasma angiotensin II/angiotensin I was closely correlated with serum active metabolite levels (r = 0.93, n = 15, P less than 0.001).