Mezavant, prolong tablets. covered. captivity. about. 1.2 g, 60 pcs.
The Mezavant tablet has a core containing 1.2 g of mesalazine in a multi-matrix system. The core is surrounded by a shell made of a copolymer of methacrylic acid and methyl methacrylate, taken in ratios (1:1) and (1:2); The composition of the shell is selected in such a way that the release of mesalazine begins only when the pH reaches about 7.
The mechanism of action of mesalazine is not fully understood, but it is believed that mesalazine (5-ASA) has a local effect, so the clinical effect of the drug does not correlate with the pharmacokinetic characteristics of the substance. The main route of elimination of mesalazine is metabolism to N-acetyl-5-aminosalicylic acid, which is pharmacologically inactive.
Suction
Studies using gamma scintigraphy have shown that after a single dose of 1.2 g of the drug by healthy volunteers on an empty stomach, mesalazine quickly and unchanged passes through the upper gastrointestinal tract. In this case, traces of an indicator labeled with a radioactive isotope are detected throughout the colon, which indicates the entry of mesalazine into these parts of the gastrointestinal tract. Complete disintegration of the Mezavant tablet and release of mesalazine was observed after approximately 17.4 hours.
After taking the drug by healthy volunteers at a dose of 2.4 g or 4.8 g 1 time / day for 14 days, the absorption of mesalazine was 21-22% of the dose taken.
After a single dose of the drug by healthy volunteers on an empty stomach at a dose of 1.2 g, 2.4 g and 4.8 g, the concentration of mesalazine in plasma was determined 2 hours (median) after administration and reached a maximum value after 9-12 hours (median). Pharmacokinetic parameters were characterized by wide variability between patients. The systemic exposure level (AUC) of mesalazine when taking the drug in the range from 1.2 g to 4.8 g was proportional to the dose taken. Cmax of mesalazine in plasma in the dose range from 1.2 g to 2.4 g increased approximately directly proportionally, while from 2.4 g to 4.8 g it increased proportionally to the dose, but to a lesser extent.
In a pharmacological study of single and multiple doses of the drug at a dose of 2.4 g and 4.8 g with regular food, mesalazine was detected in the blood plasma after 4 hours, Cmax was achieved 8 hours after a single dose. At steady state (which was usually achieved after dosing for 2 days), 5-ASA accumulation was 1.1 and 1.4 times higher for doses of 2.4 g and 4.8 g, respectively, than with a single dose.
A single dose of Mezavant 4.8 g with a fatty meal was accompanied by a slower absorption phase. Under these conditions, mesalazine was detected in the blood plasma approximately 4 hours after administration. However, a high-fat meal increased systemic mesalazine exposure (mean Cmax by 91%, mean AUC by 16%) compared with fasting levels.
In a pharmacokinetic study, healthy volunteers of both sexes (n=71, 28 young (18-35 years), 28 elderly (65-75 years) and 15 over 75 years) took Mezavant in a single dose of 4.8 g on an empty stomach. Increasing age was accompanied by an approximately 2-fold increase in systemic exposure of mesalazine and its metabolite N-acetyl-5-aminosalicylic acid (calculated based on AUC0-t, AUC0-∞ and Cmax), but did not affect the proportion of mesalazine absorbed. Increasing age was accompanied by a slowing of the apparent T1/2 of mesalazine, although the variability between patients was pronounced.
Distribution
Mezavant is believed to have a similar distribution profile to other mesalazine-containing drugs. Mesalazine has a relatively small Vd of approximately 18 L, indicating minimal systemic distribution. When the concentration of mesalazine in blood plasma in vitro was up to 2.5 μg/ml and the concentration of N-acetyl-5-aminosalicylate was up to 10 μg/ml, binding to plasma proteins was 43% and 78-83%, respectively.
Metabolism
The only important metabolite of mesalazine is the pharmacologically inactive N-acetyl-5-aminosalicylic acid. It is formed under the action of N-acetyltransferase-1 in liver cells and the cytosol of intestinal mucosal cells.
Removal
Absorbed mesalazine is excreted mainly by the kidneys after acetylation to N-acetyl-5-aminosalicylic acid. However, the drug is excreted in small quantities by the kidneys and unchanged. Less than 8% of the absorbed dose of mesalazine (21-22% of the dose taken is absorbed) is excreted unchanged in the urine within 24 hours, while more than 13% is excreted as N-acetyl-5-aminosalicylic acid. The apparent terminal half-life of mesalazine and its main metabolite after taking the drug at a dose of 2.4 and 4.8 g averaged 7-9 and 8-12 hours, respectively.
Pharmacokinetics in special groups of patients
Patients with liver failure. There are no data on the use of Mezavant in patients with liver failure. After a single dose of Mezavant at a dose of 4.8 g, the systemic exposure of mesalazine in elderly patients (over 65 years of age, average clearance 68-76 ml/min) exceeded that in younger patients (18-35 years, average clearance 124 ml/min) by up to 2 once.
Patients with renal failure. Systemic exposure in individual analysis was inversely correlated with renal function assessed by CK.
Elderly patients. After a single dose of Mezavant at a dose of 4.8 g, the systemic exposure of mesalazine increased in elderly patients (over 65 years of age) compared to younger patients by up to 2 times. Individual values of systemic exposure correlated inversely with renal function, which was assessed by CC. The potential impact of age on the safety of mesalazine should be considered in clinical practice in elderly patients. In patients with renal failure, the elimination rate and systemic concentration of mesalazine may be reduced, which may be accompanied by an increased risk of adverse renal reactions.
Mezavant in Moscow
The Mezavant tablet has a core containing mesalazine (5-aminosalicylic acid, 5-ASA) in a multicomponent matrix. The core is surrounded by a shell of methacrylic acid copolymers of types A and B; The coating is designed so that the release of mesalazine begins only when the pH reaches above 7.
The mechanism of action of mesalazine is not fully understood, but it is believed that mesalazine (5-ASA) has a local effect, so the clinical effect of the drug does not correlate with the pharmacokinetic characteristics of the substance. The main route of elimination of mesalazine is metabolism to N-acetyl-5-aminosalicylic acid, which is pharmacologically inactive.
Suction
Studies using γ-scintigraphy have shown that after a single dose of 1.2 g of the drug by healthy volunteers on an empty stomach, mesalazine quickly and unchanged passes through the upper gastrointestinal tract. In this case, traces of 14C-labeled mesalazine are detected throughout the colon, which indicates the entry of mesalazine into these parts of the gastrointestinal tract. Complete disintegration of the Mezavant tablet and release of mesalazine was observed after approximately 17.4 hours.
After a single dose of 2.4 or 4.8 g to healthy volunteers for 14 days, mesalazine absorption was 21–22% of the dose taken.
After a single dose of the drug by healthy volunteers on an empty stomach at a dose of 1.2; 2.4 and 4.8 g, the concentration of mesalazine in plasma was determined 2 hours after administration and reached its maximum value after 9–12 hours. Pharmacokinetic parameters showed wide variability. The level of systemic exposure of mesalazine - AUC - when taking the drug in the range from 1.2 to 4.8 g was proportional to the dose taken. Cmax of mesalazine in plasma in the dose range from 1.2 to 2.4 g increased approximately in direct proportion, while from 2.4 to 4.8 g it increased less than increasing doses.
When studying single and multiple doses of the drug at a dose of 2.4 and 4.8 g with regular food, mesalazine was detected in the blood plasma after 4 hours, reaching Cmax 8 hours after a single dose.
A single dose of Mezavant 4.8 g with a fatty meal was accompanied by a slower absorption phase. Under these conditions, mesalazine was detected in the blood plasma approximately 6 hours after administration. However, a high-fat meal increased systemic mesalazine exposure (mean Cmax by 91%, mean AUC by 16%) compared with fasting levels.
Distribution
Mezavant is believed to have a similar distribution profile to other mesalazine-containing drugs. Mesalazine has a relatively small Vd of approximately 18 L, indicating minimal systemic distribution. At mesalazine plasma concentrations of up to 2.5 μg/ml and N-acetyl-5-aminosalicylate concentrations of up to 10 μg/ml, the substances were bound to plasma proteins by 43 and 78–83%, respectively.
Metabolism
The only important metabolite of mesalazine is the pharmacologically inactive N-acetyl-5-aminosalicylic acid. It is formed under the action of N-acetyltransferase-1 in liver cells and the cytosol of intestinal mucosal cells.
Removal
Absorbed mesalazine is excreted mainly by the kidneys after acetylation to N-acetyl-5-aminosalicylic acid. However, the drug is excreted in small quantities by the kidneys and unchanged. Of the 21–22% of the absorbed dose of the drug, less than 8% of mesalazine is excreted unchanged in the urine within 24 hours. About 13% is excreted within 4 hours in the form of N-acetyl-5-aminosalicylic acid. The apparent T1/2 of mesalazine and its main metabolite after taking the drug at a dose of 2.4 and 4.8 g averaged 7–9 and 8–13 hours, respectively.
Special categories of patients
There are no data on the use of Mezavant in patients with impaired liver function. After a single dose of Mezavant 4.8 g, systemic exposure of mesalazine in elderly patients (over 65 years of age, mean creatinine clearance 68–76 ml/min) was greater than that in younger patients (18–35 years, mean creatinine clearance 124 ml/min). min) up to 2 times. The level of systemic exposure is inversely proportional to renal function, assessed by creatinine clearance. This should be taken into account when treating elderly patients with Mezavant.
In patients with impaired renal function, a decrease in the rate of elimination and an increase in the concentration of mesalazine in the blood plasma may be observed, which may be accompanied by an increased risk of unwanted adverse reactions from the urinary system.
In women, the AUC of mesalazine was 2 times greater than in men.
Based on limited pharmacokinetic data, the pharmacokinetics of 5-ASA and N-acetyl-5-ASA are believed to be similar in Southern European and Hispanic subjects.
