use. the mechanism of the difference is unknown. the increase in prolactin levels observed with the two drugs was much greater in women than in men. this appears to be due to the higher estrogen levels in women, as estrogen stimulates prolactin secretion from the pituitary gland. for comparison, normal prolactin levels in women are less than 20 ng/ml, prolactin levels peak at 100 to 300 ng/ml at parturition in pregnant women, and in lactating women, prolactin levels have been found to be 90 ng/ml at 10 days postpartum and 44 ng/ml at 180 days postpartum. absorption the absolute bioavailability of domperidone is low (13–17% or approximately 15%). this is due to extensive first-pass metabolism in the intestines and liver. conversely, its bioavailability is high via intramuscular injection (90%). the onset of action of domperidone taken orally is about 30 to 60 minutes. peak levels of domperidone following an oral dose occur after about 60 minutes. domperidone exposure increases proportionally with doses in the 10 to 20 mg dose range. there is a 2- to 3-fold accumulation in levels of domperidone with frequent repeated oral administration of domperidone (four times per day (every 5 hours) for 4 days). the oral bioavailability of domperidone is somewhat increased and time to peak slightly increased when it is taken with food and bioavailability is decreased by prior concomitant administration of cimetidine and sodium bicarbonate. distribution the plasma protein binding of domperidone is 91 to 93%. the tissue distribution of domperidone based on animal studies is wide, but concentrations are low in the brain. the drug is a substrate for the p-glycoprotein (abcb1) transporter, and animal studies suggest that this is the reason for the low central nervous system penetration of domperidone. small amounts of domperidone cross the placenta in animals. metabolism domperidone is extensively metabolized in the liver and intestines with oral administration. this occurs via hydroxylation and n-dealkylation. domperidone is almost exclusively metabolized by cyp3a4/5, though minor contributions by cyp1a2, cyp2d6, and cyp2c8 have been reported. cyp3a4 is the major enzyme involved in the n-dealkylation of domperidone, while cyp3a4, cyp1a2, and cyp2e1 are involved in its aromatic hydroxylation. all of the metabolites of domperidone are inactive as d2 receptor ligands. overall and peak levels of domperidone are increased by about 2.9- and 1.5-fold in moderate hepatic impairment, respectively. elimination domperidone is eliminated 31% in urine and 66% in feces. the proportion of domperidone excreted unchanged is small (10% in feces and 1% in urine). the elimination half-life of domperidone is about 7 to 9 hours in healthy individuals. however, the elimination half-life of domperidone can be prolonged to 20 hours in people with several renal dysfunction. chemistry domperidone is a benzimidazole derivative and is structurally related to butyrophenone neuroleptics like haloperidol. history domperidone was synthesized at janssen pharmaceutica in 1974 following their research on antipsychotic drugs. janssen pharmacologists discovered that some of antipsychotic drugs had a significant effect on dopamine receptors in the central chemoreceptor trigger zone that regulated vomiting, and started searching for a dopamine antagonist that would not pass the blood–brain barrier, thereby being free of the extrapyramidal side effects that were associated with drugs of this type. this led to the discovery of domperidone as a strong antiemetic with minimal central effects. domperidone was patented in the united states in 1978, with the patent filed in 1976. in 1979, domperidone was first marketed, under the brand name motilium, in switzerland and west germany. domperidone was subsequently introduced in the forms of orally disintegrating tablets (based on zydis technology) in 1999. janssen pharmaceutical has brought domperidone before the united states federal drug administration (fda) several times, including in the 1990s, but it has not been approved. in april 2014, the co-ordination group for mutual recognition and decentralised procedures – human (cmdh) published official press-release suggesting to restrict the use of domperidone-containing medicines. it also approved earlier published suggestions by pharmacovigilance risk assessment committee (prac) to use domperidone only for treating nausea and vomiting and reduce maximum daily dosage to 10 mg. society and culture generic names domperidone is the generic name of the drug and its inn, usan, ban, and jan. regulatory approval it was reported in 2007 that domperidone is available in 58 countries, including canada, but the uses or indications of domperidone vary between nations. in italy it is used in the treatment of gastroesophageal reflux disease and in canada, the drug is indicated in upper gastrointestinal motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents. in the united kingdom, domperidone is only indicated for the treatment of nausea and vomiting and the treatment duration is usually limited to 1 week. in the united states, domperidone is not currently a legally marketed human drug and it is not approved for sale in the united states. on 7 june 2004, fda issued a public warning that distributing any domperidone-containing products is illegal. it is available over-the-counter to treat gastroesophageal reflux and functional dyspepsia in many countries, such as ireland, the netherlands, italy, south africa, mexico, india, chile, and china. domperidone is not generally approved for use in the united states. there is an exception for use in people with treatment-refractory gastrointestinal symptoms under an fda investigational new drug application. formulations formulations nation manufacturer brand formulations australiajanssen–cilagmotilium10 mg scored tablets belgium and the netherlands-motiliumfrom 2013 only by prescription in belgium. bangladeshsquaremotigut10 mg scored tablets bangladeshorion pharmacosy10 mg scored tablets bangladeshastra pharmadomperon10 mg scored tablets bangladesh-ridon- canada-motilium (1985–2002)generic brands available francejanssenmotilium10 mg tablets only with prescription generic domperidone available greecejohnson & johnson hellascilroton10 mg scored tablets indiasalius pharmaescacid dxrpantoprazole 40 mg and domperidone sr 30 mg indiafdc pharmaceuticalspepcia-drabeprazole 20 mg and domperidone sr 30 mg indiarhubarb pharmaceuticals-domperidone 5, 10 and 20 mg tablets. indiaipca laboratories, mumbaidomperi suspensiondomperidone 1 mg/ml, 30 ml suspension. indiatorrent pharmaceuticalsdomstal- indiaozone pharmaceuticals and chemicalspantazone-d10 mg domperidone and 40 mg pantoprazole indiachimak health carepancert d10 mg domperidone and 40 mg pantoprazole indiadraavin pharmadraaci-xdpantaprazole 40 mg and domperione 30 mg iranabidi pharmaceutical co.motidon10 mg tablet irelandmcneil healthcaremotilium10 mg orally disintegrating tablet (odt) italy-peridondomperidone 10 mg tablets; 30 ml suspension lithuaniajohnson & johnsonmotilium- pakistanbarrett hodgson pakistandomel pakistanjohnson & johnson pakistanmotilium-vdomperidone 10 mg tablets; 30 ml suspension pakistanatco laboratories limitedvomiluxdomperidone 10 mg tablets pakistanaspin pharma (pvt) limitedmotiliumdomperidone 10 mg tablets philippineshealth saver pharmaabdopen- philippinesunited laboratories, inc.gi norm- philippinesglorious dexa mandayavometadomperidone 1 mg/ml oral suspension, 1 mg/ml oral drops philippinesglorious dexa mandayavometa ftdomperidone 10 mg fast-melting tablets portugalmedinfarcinetdomperidone 1 mg/ml oral suspension (200 ml) russiajanssen pharmaceuticamotiliumdomperidone 10 mg film-coated tablets & odt; 1 mg/ml suspension (100 ml) -obl pharmpassagixdomperidone 10 mg film-coated tablets & chewable tablets -dr. reddy's laboratoriesomez ddomperidone/omeprazole (10 mg/10 mg) saudi arabiajamjoom pharmaceuticalsdompydomperidone 10 mg tablets spain laboratorios dr. esteve, sa motilium domperidone 1 mg/ml oral suspension (200 ml) swedenebb medicaldomperidon ebb (2013)domperidone 10 mg odt and peppermint syrian arab republicoubari pharmamotindomperidone 10 mg tablets and 1 mg/ml oral suspension taiwan-dotitone- thailand-motilium m- turkeysabamotinorm- -glaxosmithklinemotinorm- research domperidone has been studied as a potential hormonal contraceptive to prevent pregnancy in women.