Pharmacology Of Moexipril

Indication For the treatment of hypertension.
Pharmacodynamics Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.
Mechanism of action Moexipril is a prodrug for moexiprilat, which inhibits ACE in humans and animals. The mechanism through which moexiprilat lowers blood pressure is believed to be primarily inhibition of ACE activity. ACE is a peptidyl dipeptidase that catalyzes the conversion of the inactive decapeptide angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor that also stimulates aldosterone secretion by the adrenal cortex and provides negative feedback on renin secretion. ACE is identical to kininase II, an enzyme that degrades bradykinin, an endothelium-dependent vasodilator. Moexiprilat is about 1000 times as potent as moexipril in inhibiting ACE and kininase II. Inhibition of ACE results in decreased angiotensin II formation, leading to decreased vasoconstriction, increased plasma renin activity, and decreased aldosterone secretion. The latter results in diuresis and natriuresis and a small increase in serum potassium concentration (mean increases of about 0.25 mEq/L were seen when moexipril was used alone). Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of moexipril remains to be elucidated. Although the principal mechanism of moexipril in blood pressure reduction is believed to be through the renin-angiotensin-aldosterone system, ACE inhibitors have some effect on blood pressure even in apparent low-renin hypertension.
Absorption Moexipril is incompletely absorbed, with bioavailability as moexiprilat of about 13% compared to intravenous (I.V.) moexipril (both measuring the metabolite moexiprilat), and is markedly affected by food, which reduces Cmax and AUC by about 70% and 40%, respectively, after the ingestion of a low-fat breakfast or by 80% and 50%, respectively, after the ingestion of a high-fat breakfast.
Volume of distribution
  • 183 L
Protein binding Moexiprilat is approxomately 50% protein bound.
Metabolism Rapidly converted to moexiprilat, the active metabolite. Conversion to the active metabolite is thought to require carboxyesterases and is likely to occur in organs or tissues, other than the gastrointestinal tract, in which carboxyesterases occur. The liver is thought to be one site of conversion, but not the primary site.
Route of elimination Moexiprilat undergoes renal elimination.
Half life Moexipril elimination half-life is approximately 1 hour. Moexiprilat elimination half-life is 2 to 9 hours.
Clearance
  • 441 mL/min
Toxicity Human overdoses of moexipril have not been reported. In case reports of overdoses with other ACE inhibitors, hypotension has been the principal adverse effect noted. Single oral doses of 2 g/kg moexipril were associated with significant lethality in mice. Rats, however, tolerated single oral doses of up to 3 g/kg. Common adverse effects include cough, dizziness, diarrhea, flu syndrome, fatigue, pharyngitis, flushing, rash, and myalgia