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lüll An overview of the clinical pharmacology of enalapril Davies RO; Gomez HJ; Irvin JD; Walker JFBr J Clin Pharmacol 1984[]; 18 Suppl 2 (Suppl 2): 215S-229SEnalapril maleate is a prodrug which when administered orally is hydrolysed to release the active converting enzyme inhibitor enalaprilat. Enalapril maleate is 60% absorbed and 40% bioavailable as enalaprilat. Both compounds undergo renal excretion without further metabolism. The functional half-life for accumulation of enalaprilat is 11 h, and this is increased in the presence of a reduction in renal function. Inhibition of converting enzyme inhibition is associated with reductions in plasma angiotensin II and plasma aldosterone, and with increases in plasma renin activity and plasma angiotensin I. Acute and chronic effects have been reviewed. When given with hydrochlorothiazide, enalapril attenuates the secondary aldosteronism and ameliorates the hypokalaemia from diuretics. Both acutely and chronically in patients with essential hypertension, enalapril reduced blood pressure with a rather flat dose-response curve. No evidence of a triphasic response such as seen with captopril has been demonstrated with enalapril, and blood pressure returns smoothly to pretreatment levels when the drug is abruptly discontinued. Once- or twice-daily dosing gives similar results. The antihypertensive effects of enalapril are potentiated by hydrochlorothiazide. Haemodynamically, blood pressure reduction is associated with a reduced peripheral vascular resistance and an increase in cardiac output and stroke volume with little change in heart rate. Renal vascular resistance decreases, and renal blood flow may increase without an increase in glomerular filtration in patients with normal renal function. In patients with essential hypertension and glomerular filtration rates below 80 ml/min/m2, both renal blood flow and glomerular filtration rates may increase.|Aldosterone/blood[MESH]|Angiotensin I/blood[MESH]|Angiotensin II/blood[MESH]|Angiotensin-Converting Enzyme Inhibitors[MESH]|Bradykinin/metabolism[MESH]|Dipeptides/blood/*pharmacology/urine[MESH]|Drug Administration Schedule[MESH]|Enalapril[MESH]|Enalaprilat[MESH]|Heart Failure/drug therapy[MESH]|Heart Rate/drug effects[MESH]|Humans[MESH]|Hydrochlorothiazide/pharmacology[MESH]|Hypertension/*drug therapy/physiopathology[MESH]|Kidney Failure, Chronic/metabolism[MESH]|Kidney/drug effects[MESH]|Norepinephrine/blood[MESH]|Prostaglandins/metabolism[MESH]|Renal Circulation/drug effects[MESH]|Renin/blood[MESH] |