Emetrol (domperidone) is a dopamine antagonist with antiemetic properties. Emetrol poorly penetrates the blood-brain barrier (BBB). The use of domperidone is very rarely accompanied by extrapyramidal side effects, especially in adults, but domperidone stimulates prolactin production by the pituitary gland. Its antiemetic effect may be due to a combination of peripheral (gastrokinetic) action and antagonism to dopamine receptors in the chemoreceptor trigger zone, located outside the GEB in the area postrema. Studies on animals, as well as the low concentrations of the drug found in the brain, indicate a predominantly peripheral effect of domperidone on dopamine receptors. When administered orally in humans, domperidone increases lower esophageal sphincter pressure, improves antroduodenal motility and accelerates gastric emptying. Emetrol (domperidone) has no effect on gastric secretion. In accordance with the ICH-E14 guidelines, a study with a detailed QT study involving healthy subjects was conducted. The study included groups of placebo, active comparison drug, and positive control, and recommended and over-therapy doses (10 and 20 mg 4 times daily) were used. The prolongation QT interval prolongation observed in this study when domperidone was used according to the recommended regimen was not clinically significant.
Emetrol (domperidone) is rapidly absorbed after oral administration on an empty stomach, the maximum plasma concentration (Cmax) is reached within 30-60 minutes. Low absolute bioavailability of domperidone when taken orally (approximately 15%) is associated with extensive first-pass metabolism in the intestinal wall and liver. Despite the fact that the bioavailability of domperidone in healthy people increases when when taking the drug after meals, patients with gastrointestinal gastrointestinal tract (GIT) complaints, domperidone should be taken 15-30 minutes before meals. Decrease gastric acidity leads to decreased absorption of domperidone. Bioavailability when taken orally is reduced by prior administration of cimetidine and sodium bicarbonate. When taking the drug after a meal, to achieve maximum absorption takes longer and the area under the curve “concentration of active substance – time” (AUC) is slightly increased. When administered orally domperidone does not accumulate and does not induce its own metabolism; maximum plasma concentration is 21 ng/ml in 90 minutes after two weeks of oral administration at a dose of 30 mg per day was almost the same as the maximum plasma concentration of 18 ng/ml after the first dose.
Emetrol (domperidone) is 91-93% bound to plasma proteins. Distribution studies on animals using the drug labeled with a radioactive isotope showed significant distribution of the drug in tissues, but low concentrations in the brain. Small amounts of the drug penetrate through the placenta in rats. Domperidone undergoes rapid and extensive metabolism in the liver by hydroxylation and N-dealkylation. In vitro metabolism studies with diagnostic inhibitors showed that CYP3A4 isoenzyme is the main form of cytochrome P450 involved in N-dealkylation of domperidone, while CYP3A4, CYP1A2 and CYP2E1 isoenzymes are involved in the aromatic hydroxylation of domperidone.
Urinary and fecal excretion is 31% and 66% of the oral dose respectively. The proportion of the drug excreted unchanged is small (10% of the amount excreted in the faeces and approximately 1% of the amount excreted with the urine). The blood plasma elimination half-life after single oral administration is 7-9 hours in healthy individuals, but is longer in patients with severe renal insufficiency.