Ganaton, 50 mg 70 pcs.

Pharmacotherapeutic group – gastrointestinal motility stimulator – acetylcholine release stimulator.

The ATC code is A03FA.

Pharmacological properties

The mechanism of action

Itopride hydrochloride increases gastrointestinal motility by antagonizing D2-dopamine receptors and inhibiting acetylcholinesterase. Itopride activates the release of acetylcholine and inhibits its degradation.

Pharmacodynamics

Itopride hydrochloride also gives an antiemetic effect due to interaction with D2 receptors located in the trigger zone. Itopride caused dose-dependent suppression of vomiting induced by apomorphine.

Itopride hydrochloride activates gastric propulsive motility through antagonism of D2 receptors and dose-dependent inhibition of acetylcholinesterase activity.

Itopride hydrochloride has a specific effect on the upper gastrointestinal tract, accelerating gastric transit and improving gastric emptying.

Itopride hydrochloride has no effect on serum levels of gastrin.

Pharmacokinetics

Intopride hydrochloride is rapidly and almost completely absorbed in the GI tract. Its relative bioavailability is 60%, which is due to metabolism during first passage through the liver. Food has no effect on bioavailability. The maximum plasma concentration (Cmax) of 0.28 µg/ml is reached 0.5-0.75 h after administration of 50 mg of itopride hydrochloride.

Recurrent oral administration of itopride hydrochloride at a dose of 50-200 mg three times daily for 7 days showed linear pharmacokinetics of the drug and its metabolites, and cumulation was minimal.

Distribution

Itopride hydrochloride is 96% bound to plasma proteins, mainly to albumin. Binding to alpha1-acid glycoprotein is less than 15% of total binding.

Itoprid is actively distributed in the tissues (volume of distribution 6.1 l/kg) and is found in high concentrations in the kidneys, small intestine, liver, adrenal glands and stomach. Penetration into the brain and spinal cord is minimal. Itoprid penetrates into breast milk.

Metabolism

Itoprid undergoes active biotransformation in the liver in humans. Three metabolites have been identified, only one of which exhibits little activity that has no pharmacological significance (approximately 2-3% of that of itopride). The primary metabolite in humans is N-oxide, which is formed by oxidation of the quaternary amino-N-dimethyl group.

Itoprid is metabolized by the action of flavin-dependent monooxygenase (FMO3). The number and efficiency of FMO isoenzymes in humans can vary depending on the genetic polymorphism, which in rare cases leads to the development of an autosomal recessive condition known as trimethylaminuria (fish-smell syndrome). In patients with trimethylaminuria, the half-life of ithopride is prolonged.

According to in vivo pharmacokinetic studies, itoprid has no inhibitory or inducing effect on CYP2C19 and CYP2E1. Therapy with itopride has no effect on CYP or uridine diphosphate glucuronidyltransferase activity.

Itopride hydrochloride and its metabolites are excreted mainly in the urine. Renal excretion of ithopride and its N-oxide after a single oral administration of the drug in therapeutic doses in healthy subjects was 3.7% and 75.4%, respectively. The terminal period of semi-elimination of itopride hydrochloride is about 6 hours.

Indications

Active ingredient

Composition

1 tablet contains:

The active ingredient:

itopride hydrochloride – 50 mg;

Associates:

Lactose – 34.975 mg (including excess due to loss in weight during manufacture – 2.93%),

corn starch – 15 mg,

carmellose – 20 mg,

Anhydrous silicic acid – 4 mg,

Magnesium stearate – 1 mg,

hypromellose – 4.4 mg,

/p>

macrogol 6000 – 0.4 mg,

titanium dioxide – 0.2 mg,

carnauba wax – 0.025 mg.

How to take, the dosage

Interaction

A metabolic interaction is unlikely, because itoprid is metabolized by flavin monooxygenase and not by CYP450.

In concomitant use of warfarin, diazepam, diclofenac sodium, ticlopidine hydrochloride, nifedipine and nicardipine hydrochloride no changes in protein binding were observed.

Itopride increases gastric motility, so it may affect the absorption of other drugs that are prescribed orally. Particular caution should be exercised when using drugs with a low therapeutic index, as well as forms with delayed release of the active substance or drugs with an enteric coating.

The anti-ulcer agents, such as cimetidine, ranitidine, teprenone and cetraxate, do not affect the prokinetic effect of itopride.

Anticholinergic agents may weaken the effects of itopride.

Special Instructions

With regard to enhancing the isoprid action of acetylcholine, caution should be exercised when prescribing because of the possible development of cholinergic adverse reactions in patients for whom this may aggravate the underlying disease.

Synopsis

Contraindications

Cautious use

Because of the increased isoprid action of acetylcholine, caution should be exercised because of possible cholinergic adverse reactions in the category of patients for whom their occurrence may aggravate the underlying disease.

Side effects

Blood and lymphatic system disorders: leukopenia, thrombocytopenia.

Allergic reactions: skin hyperemia, skin itching, rash, anaphylaxis.

Endocrine disorders: increase in prolactin levels, gynecomastia.

Nervous system disorders: dizziness, headache, tremor.

Gastrointestinal disorders: diarrhea, constipation, abdominal pain, increased salivation, nausea, jaundice.

Laboratory changes: increase of aspartate aminotransferase (ACT), alanine aminotransferase (ALT), gammaglutamyl transpeptidase, alkaline phosphatase activity and bilirubin level.

Overdose

Pregnancy use

Similarities