Toridon Mechanism of Action

Pharmacology: Pharmacodynamics: Domperidone is a dopamine antagonist with antiemetic properties, Domperidone does not readily cross the blood brain barrier. In domperidone users, especially in adults, extrapyramidal side effects are very rare, but domperidone promotes the release of prolactin from the pituitary. Its antiemetic effect may be due to a combination of peripheral (gastrokinetic) effects and antagonism of dopamine receptors in the chemoreceptor trigger zone, which lies outside the blood brain barrier in the area postrema.
Pharmacokinetics: Absorption: The systemic bioavailability of domperidone is only about 15% in fasting subjects given a dose by mouth, although this is increased when domperidone is given after food. The low bioavailability is thought to be due to first-pass hepatic and intestinal metabolism. The bioavailability of rectal domperidone is similar to that following oral administration, although peak plasma concentrations are only achieved after about an hour, compared with 30 minutes after a dose by mouth.
Distribution: Domperidone is more than (90%) bound to plasma protein. It does not readily cross the blood-brain barrier. Small amounts of domperidone are distributed into breast milk, reaching concentrations about one-quarter of those in maternal serum.
Metabolism: Domperidone undergoes rapid and extensive hepatic metabolism. The main metabolic pathways are N-dealkylation and by cytochrome P450 isoenzyme CYP3A4, and aromatic hydroxylation by CYP3A4, CYP1A2, and, CYP2E1.
Excretion: About 30% of an oral dose is excreted in urine within 24 hours, almost entirely as metabolites; the remainder of a dose is excreted in feces over several days, about 10% as unchanged drug. It has a terminal elimination half-life of about 7.5 hours.