| 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 |
|
| 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 |
|
| 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 |
