Listata, 120 mg 20 pcs.

Pharmacodynamics

Orlistat is a potent, specific and reversible inhibitor of gastrointestinal lipases with prolonged action. Its therapeutic action is carried out in the lumen of the stomach and small intestine and consists in the formation of covalent bonding with the active serine site of gastric and pancreatic lipases.

Inactivated enzyme thereby loses the ability to break down food fats coming in the form of triglycerides, into absorbed free fatty acids and monoglycerides. Since unchecked triglycerides are not absorbed, the resulting decrease in the intake of calories into the body leads to a decrease in body weight. Thus, the therapeutic action of the drug is carried out without absorption into the systemic blood flow.

Judging by the results of fecal fat content the action of orlistat starts 24-48 hours after intake. After discontinuation of orlistat, fecal fat content in 48-72 h usually returns to pre-therapy levels.

Clinical efficacy

Patients taking orlistat show greater weight loss compared to patients on diet therapy. Weight loss begins within the first 2 weeks of starting treatment and continues for 6 to 12 months, even in patients with a negative response to diet therapy. Over 2 years, there is a statistically significant improvement in the profile of metabolic risk factors associated with obesity. In addition, there is a significant decrease in body fat compared to placebo administration. Orlistat is effective in preventing weight gain again. Re-gain of body weight, not more than 25% of the lost weight, is observed in about half of the patients, and in half of these patients re-gain of body weight is not observed or even further weight loss is noted.

In patients with overweight or obesity and type 2 diabetes, taking orlistat for 6 months to 1 year, there is greater weight loss compared to patients receiving diet therapy alone. The weight loss is mainly due to a decrease in body fat. During orlistat therapy, a statistically and clinically significant improvement in glycemic control is observed. In addition, against the background of treatment with orlistat there is a decrease in the dose of hypoglycemic agents, insulin concentration, as well as a decrease in insulin resistance.

When using orlistat for 4 years the risk of developing type 2 diabetes is significantly reduced (by about 37% compared to placebo). The degree of risk reduction is even more significant in patients with initial impaired glucose tolerance (approximately by 45%).

Maintenance of body weight at the new level is observed during the whole period of the drug use.

When orlistat was used for 1 year in adolescents with obesity, a decrease in BMI, fat mass, as well as waist and hip circumference was observed compared to the placebo group. Also, patients treated with orlistat showed a significant decrease in diastolic BP compared to the placebo group.

Pharmacokinetics
Absorption

In volunteers with normal body weight and obesity, the systemic effects of orlistat are minimal. After a single oral dose of 360 mg unchanged orlistat is not detected in plasma, which means that its concentrations are below the limit of quantification (less than 5 ng/ml).

In general, after therapeutic doses unchanged orlistat was detected in plasma only in rare cases, and its concentrations were extremely low (less than 10 ng/ml or 0.02 μmol). There are no signs of cumulation, which confirms that absorption of orlistat is minimal.

Distribution

Vd cannot be determined because orlistat is very poorly absorbed. In vitro orlistat is more than 99% bound to plasma proteins (mainly lipoproteins and albumin). In minimal amounts orlistat can penetrate into erythrocytes.

Metabolism

Metabolism of orlistat is carried out mainly in the intestinal wall. In obese patients, approximately 42% of the minimal fraction of orlistat that undergoes systemic absorption is accounted for by two major metabolites, M1 (a four-member hydrolyzed lactone ring) and M3 (M1 with a detached N-formylleucine residue).

M1 and M3 molecules have an open b-lactone ring and inhibit very weakly lipase (1000 and 2500 times weaker than orlistat, correspondingly).

Given this low inhibitory activity and low plasma concentrations (26 ng/ml and 108 ng/ml on average, respectively) after therapeutic doses, these metabolites are considered pharmacologically inactive.

Excretion

In persons with normal and excess body weight, the major route of excretion is the excretion of unabsorbed orlistat through the intestine. About 97% of the administered dose is excreted through the intestine, with 83% as unchanged orlistat.

The total renal excretion of all substances structurally related to orlistat is less than 2% of the administered dose. The time to complete excretion of orlistat from the body (through the intestine and the kidneys) is 3-5 days. The ratio of orlistat excretion routes in normal and overweight volunteers was similar. Both orlistat and its metabolites M1 and M3 can be excreted with bile.

Pharmacokinetics in special clinical groups

Plasma concentrations of orlistat and its metabolites (M1 and M3) in children do not differ from those in adults when comparing the same doses of orlistat. Daily excretion of fat with feces is 27% of intake with food during orlistat therapy.

Indications

Active ingredient

How to take, the dosage

Interaction

Special Instructions

Contraindications

Side effects

Overdose

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