Enalapril (MK421) and its lysine analogue (MK521): a comparison of acute and chronic effects on blood pressure, renin-angiotensin system and sodium excretion in normal man.

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Abstract
The immediate and long‐term effects of enalapril (MK421) and its lysine analogue (MK521) in once‐daily dosage, were compared in a study of 12 normal subjects. Both compounds lowered blood pressure equally throughout 24 h without causing tachycardia. The biochemical changes with MK521 were more sustained than with MK421, but this did not affect the magnitude of blood pressure reduction. Twenty‐four hours after the previous dose, with both active drugs, plasma renin concentration was significantly higher on day 8 than on day 1, though angiotensin I did not increase in proportion; this probably reflects a fall in renin‐ substrate with prolonged converting enzyme inhibition. There was an early natriuresis with each compound but this effect was no longer apparent after 8 days of continuous therapy. Both MK421 and MK521 were well tolerated with no serious side effects.