The drug emetrol for vomiting and to stimulate peristalsis includes the active ingredient domperidone.
Emetrol (Domperidone) is a dopamine antagonist with antiemetic properties. Domperidone penetrates through the blood-brain barrier to a small extent. Domperidone use is very rarely accompanied by extrapyramidal side effects, especially in adults, but domperidone stimulates prolactin release from 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, which is outside the blood-brain barrier in the posterior region. Animal studies, as well as the low concentrations detected in the brain, indicate a predominantly peripheral effect of domperidone on dopamine receptors.
Studies in humans have shown that when taken orally, domperidone increases pressure in the lower esophagus, improves antroduodenal motility, and accelerates gastric emptying. Domperidone has no effect on gastric secretion.
Absorption. Emetrol (Domperidone) is rapidly absorbed when taken orally on an empty stomach, the maximum plasma concentration is reached after about 60 minutes. Low absolute bioavailability of oral domperidone (about 15%) is due to extensive first-pass metabolism in the intestinal wall and the liver. Although in healthy subjects the bioavailability of domperidone is increased when taken after meals, patients with gastrointestinal complaints should take domperidone 15-30 minutes before meals. Reduced gastric acidity decreases the absorption of domperidone. When taking the drug orally after a meal, maximum absorption is slightly delayed.
Distribution. When administered orally, domperidone does not accumulate and does not induce its own metabolism; maximum plasma levels after 90 minutes (21 ng/ml) after two weeks of oral administration of 30 mg per day were almost the same as after the first dose (18 ng/ml). Domperidone is 91-93% bound to plasma proteins. Distribution studies of domperidone on animals using the preparation labeled with radioactive isotope showed its significant distribution in tissues, but low concentration in the brain. In animals, small amounts of the drug penetrate through the placenta.
Metabolism. Domperidone is rapidly and extensively metabolized in the liver by hydroxylation and N-dealkylation. In vitro metabolism studies with diagnostic inhibitors have shown that CYP3A4 is the major form of cytochrome P450 involved in N-dealkylation of domperidone, while CYP3A4, CYP1A2 and CYP2E1 take part in aromatic hydroxylation of domperidone.
Excretion. Excretion with urine and feces is 31% and 66% of the oral dose, respectively. Excretion of the drug unchanged is a small percentage (10% in the feces and approximately 1% in the urine). The blood plasma elimination half-life after a single dose is 7-9 hours in healthy volunteers, but it is prolonged in patients with severe renal insufficiency.