Pharmacology: Lisinopril is an inhibitor of the angiotensin-converting enzyme. The angiotensin converting enzyme (ACE) is a peptidyl dipeptidase, which catalyses the conversion of angiotensin I into the vasoconstricting peptide, angiotensin II. Inhibition of ACE results in a lower concentration of plasma angiotensin II, which causes an increase of the plasma renin activity (caused by the elimination of the negative feedback of angiotensin II on the renin secretion) and reduced aldosterone secretion.
ACE is identical with kininase II. That is why lisinopril can block bradykinin, a strong vasodepressive peptide. Although it is still not clear, which part this plays in the therapeutic effect of lisinopril.
Although the blood pressure reducing mechanism of lisinopril supposedly works primarily by suppression of the renin-angiotensin-aldosterone system, which plays an essential role in the blood pressure regulation, lisinopril has an antihypertensive effect also in patients with a low plasma renin level.
Pharmacokinetics: In clinical trials the maximum plasma concentration was achieved within about 7 hours of oral administration. Patients with an acute myocardial infarction showed a tendency towards a slightly longer time to peak plasma concentration. With repeated doses lisinopril proved to have an effective half-life of 12.6 hours.
The major part of the active agent is eliminated during the early phase, in lower concentrations a prolonged terminal elimination follows, which, however, does not lead to accumulation of the drug. This terminal phase is most likely based on a saturated binding to ACE and is not proportional to the applied dose. It seems that lisinopril will not bind to other serum proteins.
Reduced kidney function reduces the renal elimination of lisinopril. This becomes clinically significant when the glomerular filtration rate is <60ml/min. Elderly patients have higher blood levels and higher AUC values than younger patients. Lisinopril can be removed by dialysis.
Measurements of urine elimination in clinical trials have shown that the average absorbed part of lisinopril is about 29% (25-50%), with an interindividual variation of (6-60%) at all dosages tested (5-80mg).
Lisinopril is not metabolised and the absorbed substance is eliminated completely and unchanged in the urine. The absorption of lisinopril is not affected by the simultaneous intake of food.