Enalaprilat: an intravenous substitute for oral enalapril therapy. Humoral and pharmacokinetic effects.
Thirteen subjects with essential hypertension controlled on oral enalapril (20 mg/day) therapy were entered into a protocol to assess serially 24-hour blood pressure, the renin-angiotensin-aldosterone system, angiotensin-converting enzyme activity, and plasma and urine enalaprilat drug levels, following both chronic oral administration of enalapril and its replacement with intravenous enalaprilat. Results indicate that systolic and diastolic blood pressures remain well controlled following cessation of oral enalapril and replacement with intravenous enalaprilat. Enalaprilat drug levels, following oral enalapril and intravenous enalaprilat, remained above the therapeutic levels required for angiotensin-converting enzyme inhibition. However, therapeutic enalaprilat levels can probably be achieved with one fourth of the total cumulative dose of enalapril, administered as enalaprilat at 6-hour intervals. Intravenous enalaprilat stimulated plasma renin activity and decreased immunoreactive plasma angiotensin II and plasma aldosterone concentrations. However, immunoreactive plasma angiotensin II concentrations were not suppressed below pretreatment values, suggesting that chronic enalapril/acute enalaprilat therapy controls blood pressure through a nonangiotensin-mediated antihypertension mechanism.
D000284:Administration, Oral; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D015773:Enalaprilat; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D012083:Renin; D015773:Enalaprilat