Aceon (perindopril erbumine)

Perindopril erbumine is a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor.

Perindopril erbumine is a pro-drug for perindoprilat, which inhibits angiotensin-converting enzyme (ACE) in humans and animals. The mechanism through which perindoprilat lowers blood pressure is believed to be primarily inhibition of ACE activity. ACE is a peptidyl dipeptidase that catalyzes conversion of the inactive decapeptide, angiotensin I, to the vasoconstrictor, angiotensin II.

Angiotensin II is a potent peripheral vasoconstrictor, which stimulates aldosterone secretion by the adrenal cortex, and provides negative feedback on renin secretion. Inhibition of ACE results in decreased plasma angiotensin II, leading to decreased vasoconstriction, increased plasma renin activity, and decreased aldosterone secretion. The latter results in diuresis and natriuresis and may be associated with a small increase of serum potassium.

ACE is identical to kininase II, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of perindopril erbumine remains to be elucidated. While the principal mechanism of perindopril in blood pressure reduction is believed to be through the renin-angiotensin-aldosterone system, ACE inhibitors have some effect even in apparent low-renin hypertension.

Perindopril has been studied in relatively few Black patients, usually a low-renin population, and the average response of diastolic blood pressure to perindopril was about half the response seen in non-Black patients, a finding consistent with previous experience of other ACE inhibitors.

After administration of perindopril, ACE is inhibited in a dose- and blood concentration- related fashion, with the maximal inhibition of 80-90% attained by 8 mg persisting for 10-12 hours. Twenty-four hour ACE inhibition is about 60% after these doses. The degree of ACE inhibition achieved by a given dose appears to diminish over time.

Oral administration of perindopril results in peak plasma concentrations that occur at approximately 1 hour. The absolute oral bioavailability of perindopril is about 75%. Following absorption, approximately 30-50% of systemically available perindopril is hydrolyzed to its active metabolite, perindoprilat, which has a mean bioavailability of about 25%.

Peak plasma concentrations of perindoprilat are attained 3-7 hours after perindopril administration. Oral administration of perindopril with food does not significantly lower the rate or extent of perindopril absorption relative to the fasted state; however, the extent of biotransformation of perindopril to the active metabolite, perindoprilat, is reduced approximately 43%, resulting in a reduction in the plasma ACE inhibition curve of approximately 20%, which is probably clinically insignificant. In clinical trials, perindopril was generally administered in a non-fasting state.

Approximately 60% of circulating perindopril is bound to plasma proteins; only 10-20% of perindoprilat is bound. Therefore, drug interactions mediated through effects on protein binding are not anticipated. Perindopril is extensively metabolized following oral administration into 6 metabolites, including perindoprilat (active metabolite).

Following oral administration, only 4-12% of the dose is recovered unchanged in the urine (as metabolites). Hepatic esterase appears to be responsible for the hydrolysis of perindopril. The mean half-life of perindopril associated with most of its elimination is approximately 0.8-1 hours.

The active metabolite, perindoprilat, also exhibits multicompartment pharmacokinetics following oral administration of perindopril erbumine. Formation of perindoprilat is gradual with peak plasma concentrations occurring between 3-7 hours. The subsequent decline in plasma concentration shows an apparent mean half-life of 3-10 hours for the majority of the elimination, with a prolonged terminal elimination half-life of 30-120 hours resulting from slow dissociation of perindoprilat from plasma/tissue ACE binding sites.

During repeated oral once daily dosing with perindopril, perindoprilat accumulates about 1.5- to 2-fold and attains steady state plasma levels in 3-6 days. The clearance of perindoprilat and its metabolites is almost exclusively renal.

USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. This medication is also used to prevent heart attacks in people with a certain type of heart disease (stable coronary artery disease).

Perindopril belongs to a class of drugs known as ACE inhibitors. It works by relaxing blood vessels so blood can flow more easily.

Generic name: perindopril erbumine
Pronunciation: (per-IN-doh-prill)

The following indications are listed for Aceon:

• Hypertension
• Myocardial Infarction Prevention

Also known as: Acute Mi Prophylaxis, Acute Myocardial Infarction Prophylaxis, Ami Prophylaxis, Cardiac Infarct Prophylaxis, Cardiac Infarction Prophylaxis, Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesis, Hypertensive Disorder, Mi Prophylaxis, Myocardial Infarct Prophylaxis, Myocardial Infarction Prophylaxis, Systemic Arterial Hypertension.

No ICD codes are available for this drug.