Valsartan

Pharmacological properties

valsartan - is an active specific antagonist of angiotensin ii receptors. it acts selectively on the at1 subtype receptors responsible for the known effects of angiotensin ii. elevated plasma angiotensin ii levels after blocking the at1 receptors with valsartan can stimulate the unblocked at2 receptor, which balances the effect of the at1 receptor. valsartan does not exhibit any partial agonist activity with respect to the at1 receptor, but has a much greater (approximately 20,000-fold) affinity for the at1 receptor than at the at2 receptor.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. The use of the drug in patients with hypertension leads to a decrease in blood pressure without affecting the pulse rate.

The onset of hypotensive action is noted within 2 hours, a maximum of 4-6 hours after ingestion. After taking the drug, the antihypertensive effect persists for 24 hours. The maximum therapeutic effect develops after 2–4 weeks from the start of treatment and persists with prolonged therapy.

In the case of a combination of the drug with hydrochlorothiazide, a significant additional decrease in blood pressure is achieved.

Sudden discontinuation of the drug is not accompanied by the development of withdrawal syndrome. With prolonged use of the drug by patients with hypertension, it was found that valsartan did not have a significant effect on the level of total cholesterol, uric acid, as well as in fasting studies on the concentration of TG and glucose in blood plasma.

The use of the drug leads to a decrease in hospitalization due to heart failure, a slower progression of heart failure, an improvement in the NYHA classification functional class, an increase in the ejection fraction, as well as a decrease in the severity of symptoms of heart failure and an improvement in the quality of life compared with placebo.

Pharmacokinetics After oral administration of the drug, valsartan is absorbed rapidly, however, the degree of absorption varies significantly. The average absolute bioavailability of the drug is 23%. When using valsartan with food, AUC decreases by 48%, although, starting from about the 8th hour after taking the drug, the concentration of valsartan in blood plasma, both in the case of fasting and when taken with food, are the same. The decrease in AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect. Therefore, the drug can be taken on an empty stomach, and with food.

The pharmacokinetic curve of valsartan has a downward multiexponential nature (T_½α ≤1 h and T_½β - about 9 hours). In the range of doses studied, the kinetics of valsartan is linear. With repeated use of the drug, no changes in kinetic parameters were noted. When taking the drug 1 time per day, cumulation is negligible. Plasma concentrations in women and men were the same.

Valsartan to a large extent (94–97%) binds to plasma proteins, mainly with albumin. The volume of distribution during the equilibrium period is low (about 17 l). Compared with hepatic blood flow (about 30 l / h), plasma clearance of valsartan is relatively slow (about 2 l / h). The amount of valsartan excreted with feces is 83% of the oral dose. About 13% is excreted in urine, mainly unchanged. T_½ valsartan is 6 hours

Average time to reach C_max and T_½ Valsartan in patients with heart failure and healthy volunteers is the same. AUC and C indicators_max Valsartan increase linearly and is almost proportional to the dose increase above the clinical range (40–160 mg 2 times a day). The cumulation coefficient is on average 1.7. The clearance of valsartan after oral administration is about 4.5 l / h.Age does not affect the clearance of the drug in patients with heart failure.

Pharmacokinetics in individual patient groups

Elderly patients. In some elderly patients, the systemic effect of valsartan was more pronounced than in young patients, but no clinical significance of this was established.

Patients with impaired renal function. No correlation was found between renal function and systemic exposure to valsartan. Therefore, patients with impaired renal function (creatinine clearance of 10 ml / min) do not require dose adjustment. While there is no data on the safety of the drug in patients with creatinine clearance of 10 ml / min and in those who are on hemodialysis, therefore, valsartan should be used with caution. Valsartan has a high degree of binding to plasma proteins, so its elimination during hemodialysis is unlikely.

Patients with impaired liver function. About 70% of the absorbed dose of the drug is excreted with bile, mainly unchanged. Valsartan does not undergo significant biotransformation, the systemic effect of valsartan does not correlate with the degree of impaired liver function. It was found that in patients with biliary cirrhosis or obstruction of the biliary tract, the AUC of valsartan increases approximately 2 times.

Indications

Ag in adults and children aged ≥6 years. symptomatic heart failure in adult patients when APF inhibitors cannot be used, or as adjunctive therapy with APF inhibitors when β-adrenoreceptor blockers cannot be used.

Application

Diocor solo is taken orally, regardless of food intake, washed down with water.

Hypertension in adults

The recommended starting dose of Diocore Solo for adults is 80 mg once a day. The antihypertensive effect is achieved within 2 weeks, and the maximum effect is obvious after 4 weeks. For patients with uncontrolled blood pressure, the dose can be increased to 160 mg / day and to a maximum of 320 mg / day, additional use of diuretics is possible.

Diocor Solo can also be used simultaneously with other antihypertensive agents.

AH in children aged ≥6 years

The recommended starting dose of Diocore Solo is 40 mg once a day for children with a body weight of 35 kg and 80 mg once a day for children with a body weight of ≥35 kg. The dose should be adjusted based on the response / change in blood pressure. Possible maximum doses, which are not recommended to be exceeded, are given in the table.

Table. The maximum dose of Diocor Solo

For children with creatinine clearance of 30 ml / min and children undergoing dialysis, valsartan is not recommended due to the lack of research. Children with creatinine clearance of 30 ml / min dose adjustment is not required. Careful monitoring of renal function and serum potassium levels is required.

Diocor Solo is contraindicated in children with severe liver failure, biliary cirrhosis and cholestasis. Clinical experience with valsartan in children with mild to moderate hepatic impairment is limited. The dose of valsartan for such patients should not exceed 80 mg.

Heart failure in adults. The recommended initial dose of Diocore Solo is 40 mg 2 times a day. Increasing the dose to 80 and 160 mg 2 times a day should be carried out at intervals of at least 2 weeks, to the highest dose, depending on the patients tolerance to the drug. The maximum daily dose is 320 mg and is divided into several doses.

Valsartan can be taken in combination with other drugs used for heart failure. However, a triple combination of an ACE inhibitor, a β-adrenergic receptor blocker, and valsartan is not recommended.

Assessment of the status of patients with heart failure should always include an assessment of the state of renal function.

Note on all indications: elderly patients and adult patients