Abstract
Quantitative relationships between angiotensin converting enzyme activity in human serum and concentration of an enzyme inhibitor, the active diacid metabolite of MK-421 [N-(S-1-carbethoxy-3-phenylpropyl)-S-alanyl-S-proline maleate], were defined. Dose-response curves were generated in vitro by adding the diacid metabolite (DM) to serum (ID50 = to 6x10-9 M); l0-15% of initial activity was nonsuppressible. DM an converting enzyme activity were also measured in serum from hypertensive subjects receiving oral MK-421. The dose-response curve for serum samples following single doses of MK-421 (ID50 = 6x10-9M), was similar to curves generated in vitro while the curve for sample following chronic therapy suggested a small decrease in inhibitory potency.
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