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  • Title: Kinetic and metabolic aspects of enalapril action.
    Author: Lant AF, McNabb RW, Noormohamed FH.
    Journal: J Hypertens Suppl; 1984 Dec; 2(2):S37-42. PubMed ID: 6100875.
    Abstract:
    Enalapril is a long-acting, sulphydryl-free, ACE inhibitor whose humoral and hypotensive effects are maximal at 4-8 h and remain detectable at 24 h after a single dose. Serum profiles after chronic dosing of enalapril show little accumulation of the active diacid metabolite, enalaprilat. Comparison between the observed and predicted steady-state urinary recoveries of enalaprilat yields an effective accumulation half-life of approximately 11 h. In normotensive subjects, enalapril increases renal blood flow whilst leaving glomerular filtration unchanged irrespective of the state of sodium balance. Similarly under conditions of salt loading and salt depletion, a biphasic saluretic response is seen which parallels the excretory maxima for unchanged enalapril (1-2 h) and enalaprilat (4-8 h) suggesting direct interference by the drug moieties with tubular NaCl reabsorption. During the period of maximal enalapril action, uricosuria and phosphaturia are seen, supporting a direct action of enalaprilat on proximal tubular handling of these anions. Detailed documentation of the chronic metabolic effects of enalapril remains incomplete. A small rise in plasma potassium concentrations can occur but overt hyperkalaemia is unlikely in the absence of gross renal failure. Continued dosing is associated with a fall in plasma uric acid concentrations; plasma prolactin concentrations remain unaltered.
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