Enalapril maleate and a lysine analogue (MK‐521): disposition in man.

Abstract

1 The disposition of two angiotensin converting-enzyme inhibitor drugs was studied in normal volunteers. One drug was enalapril maleate (MK-421), which requires in vivo esterolysis to yield active inhibitor . The other was a lysine analogue of MK-422 (MK-521), which requires no bioactivation. 2 Absorption of enalapril maleate (10 mg, p.o.) was rapid, with peak serum concentrations of enalapril observed 0.5-1.5 h after administration. Based upon urinary recovery of total drug (enalapril plus MK-422), absorption was at least 61%. Bioactivation appeared to be largely post-absorptive. From the ratio of MK-422 to total drug in urine, the minimum extent of bioactivation was estimated at 0.7. 3 A similar dose of MK-521 was absorbed more slowly, reaching peak serum concentrations 6-8 h following drug administration. Minimum absorption, based upon urinary recovery, was 29%. 4 Serum concentration v time profiles for both drugs were polyphasic and exhibited prolonged terminal phases. 5 Recovery in urine and faeces of administered enalapril maleate (intact and as MK-422) was 94%. Recovery of MK-521 was 97%. These results indicate lack of significant metabolism of these agents, apart from the bioactivation of enalapril.

The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects.

“…at the time of peak enalaprilic acid plasma levels (Ulm et al, 1982) and of maximal drug-induced reduction in blood pressure in normotensive (McGregor et al, 1981;Reid et al, 1983) as well as in hypertensive patients (Gavras et al, 1982;Johnston et al, 1983). By that time, PCEA was dramatically decreased, PRA was increased and PA tended to decline.…”

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.

“…(Figure 2). It is largely inactive until absorbed and de-esterified, yielding the highly active, but poorly absorbed diacid (MK422) (Ulm et al, 1982). MK521 (the lysine analogue of MK422) is orally absorbed and requires no bioactivation.…”

The pharmacokinetics of enalapril in patients with compensated liver cirrhosis.

“…Serum ACE activity was measured by enzymatic assay (Kelly et al, 1986). Differ Enalaprilat is known to be eliminated primarily by renal excretion (Ulm et al, 1982), and renal impairment is associated with decreased excretion of the drug (Fruncillo et al, 1987;Kelly et al, 1986 …”