Lotensin (Benazepril)
Form of production, composition and packaging
Tablets, film-coated 1 tab.
benazeprila hydrochloride 5 mg
- – 20 mg
Excipients: anhydrous colloidal silicon dioxide (Aerosil 200), microcrystalline cellulose (PH Avitsel 102), hydrogenated castor oil, lactose monohydrate, maize starch, crospovidone, hydroxypropyl methylcellulose, iron oxide yellow, iron oxide red, titanium dioxide, polyethylene glycol 8000, talc.
14 – Packing calendar (1) – packs cardboard.
14 – Packing calendar (2) – packs cardboard.
Clinico-pharmacological group: ACE inhibitor
Registration № №:
# Tablets, film coated, 5 mg: 14 or 28 – P № 013879/01-2002, 29.03.02
# Tablets, film-coated, 20 mg: 14 or 28 – P № 013879/01-2002, 29.03.02 Mode of action
ACE inhibitor. Lotenzin (benazeprila hydrochloride) is a prodrug, which after hydrolysis is transformed into an active metabolite – benazeprilat that inhibits ACE and, thus, blocking the conversion of angiotensin I to angiotensin II. Thus, the reduced vasoconstrictor action of angiotensin II and its stimulating effect on the production of aldosterone, which promotes the reabsorption of sodium and water in the renal tubules, and also increases cardiac output.Lotenzin reduces peripheral vascular resistance and afterload to the heart. Due venodilatiruyuschego action Lotenzin also reduces preload and heart. Against the background of Lotenzina not observed reflex increase in heart rate in response to a decrease in total peripheral resistance.
After a single dose Lotenzina hypotensive effect observed after 1 h, reaches a maximum after 2-4 h and lasts up to 24 h. At the systematic application of a persistent reduction in blood pressure observed after 1 week. Expression of the hypotensive effect is not dependent on age, race, and initial values of plasma renin activity. With the sudden cancellation of the sharp rise of blood pressure medication is not observed.
In patients with chronic heart failure Lotenzina adherence to standard therapy resulted in an increase in cardiac output, increased exercise tolerance, reduce the pressure in the pulmonary capillary wedge, systemic arterial blood pressure and reduce symptoms of heart failure.Patients c renal dysfunction (CC 30-60 ml / min), with kidney diseases of various origins, long-term treatment Lotenzinom led to a decrease in proteinuria and the risk of further deterioration of renal function by 53%.
Pharmacokinetics
Suction
At least 37% of the accepted oral dose benazeprila hydrochloride absorbed from the gastrointestinal tract. Prodrug rapidly converted to pharmacologically active metabolite – benazeprilat. After receiving benazeprila hydrochloride fasting Smax benazeprila and benazeprilata in blood plasma is reached after 30 and 60-90 min, respectively.
After oral benazeprila hydrochloride bioavailability metabolite – benazeprilata is about 28%.Receiving tablets after a meal leads to slower absorption, but the amount absorbed and converted into benazeprilat benazeprila not changed. Therefore benazeprila hydrochloride can be taken with meals, and fasting.
In the range of doses from 5 mg to 20 mg of the value of AUC and Cmax benazeprila and benazeprilata roughly proportional to the dose. Small but statistically significant deviations from proportional to the dose recorded by using a wider range of doses – 2-80 mg. This may be due to saturable binding benazeprilata with APF.
When using multiple doses of the drug (5-20 mg 1 time /) pharmacokinetic parameters have not changed. Cumulation benazeprila not marked. Benazeprilat accumulates only to a small extent; AUC in achieving Css approximately 20% higher than after the first dose. T1 / 2 benazeprilata up 10-11 hours Css in plasma achieved after 2-3 days.
Distribution
About 95% benazeprila and benazeprilata bound to plasma proteins (mainly albumin). The degree of binding with age does not change. Benazeprilata Vd at steady state is about 9 liters.
Metabolism
Benazepril significantly metabolized. The main metabolite is benazeprilat. This transformation is expected by means of enzymatic hydrolysis, mainly in the liver. Two subsequent metabolites are conjugates atsilglyukuronidnye benazeprila and benazeprilata.
Withdrawal
Benazeprilat excreted by the kidneys and the gall to patients with normal renal function, renal excretion predominates. In the urine of benazeprila less than 1%, while the number benazeprilata – about 20% of the dose. Withdrawal from the plasma benazeprila ends after 4 h. Excretion benazeprilata two-phase flows, T1 / 2 of the initial phase (α-phase) is about 3 h, and the final phase (β-phase) – about 22 h. The presence of the final phase of launch points to the strong binding benazeprilata with ACE.
Pharmacokinetics in special clinical cases
In patients with arterial hypertension Css benazeprilata depends on the magnitude of the daily dose.
In patients with chronic heart failure benazeprila absorption and its transformation into benazeprilat not change. Due to some moderation in removing the active substance in this group of patients compared with healthy individuals or patients with arterial hypertension, Css benazeprilata somewhat higher.
Pharmacokinetic parameters benazeprila benazeprilata and the elderly, in patients with mild or moderate impaired renal function (Page 30-80 ml / min) or with nephrotic syndrome did not significantly change. In human liver (due to cirrhosis of the liver) pharmacokinetic parameters benazeprilata not change, so these patients do not need to correct dosing regime.
In severe renal insufficiency (CC <30 ml / min) slower excretion benazeprilata and, consequently, possible drug accumulation, therefore, may require lower doses. Benazepril and benazeprilat derived from the plasma even in patients with end-stage renal failure, pharmacokinetic parameters in these cases are the same as in patients with severely impaired renal function. Extrarenal clearance (eg, metabolic or excretion of bile) partially compensate for the decline in renal clearance.
Are regularly hemodialysis started, at least, after 2 h after administration benazeprila hydrochloride does not alter significantly the concentration benazeprila and benazeprilata in blood plasma. This means that the need to accept the additional dose after dialysis there. With the help of hemodialysis from the body appears only a very small amount benazeprilata.
Pharmacokinetics benazeprila hydrochloride does not change in the case of the following drugs: hydrochlorothiazide, furosemide, chlorthalidone, digoxin, atenolol, nifedipine, amlodipine, naproxen, acetylsalicylic acid or cimetidine. In turn, the use benazeprila hydrochloride does not lead to significant changes in the pharmacokinetics of these drugs.
Indications for use drugs LOTENZIN
- Arterial hypertension;
- Chronic heart failure (as part of combination therapy).
