Pharmacology: Ramipril (Amivan) is an angiotensin converting enzyme (ACE) inhibitor, which after hydrolysis to ramiprilat, blocks the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. So, inhibition of ACE by Ramipril results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and decreased aldosterone secretion. Thus, Ramipril exerts its antihypertensive activity.
Pharmacokinetics: Ramipril acts as a prodrug of the diacid ramiprilat, its active metabolite. After oral doses at least 50 to 60% is absorbed. Ramipril is metabolized in the liver to ramiprilat; other metabolites are inactive. Peak plasma concentrations of ramiprilat are achieved 2 to 4 hours after an oral dose of ramipril. Ramiprilat is about 56% bound to plasma proteins. After oral doses ramipril is excreted primarily in the urine, as ramiprilat, other metabolites, and some unchanged drug. About 40% of an oral dose appears in the faeces; this may represent both biliary excretion and unabsorbed drug. The effective half-life for accumulation of ramiprilat is 13 to 17 hours after multiple doses of ramipril 5 to 10 mg, but is much longer for doses of 1.25 to 2.5 mg daily; the difference relates to the long terminal half-life associated with saturable binding to the angiotensin-converting enzyme. The clearance of ramiprilat is reduced in renal impairment.