Chemical formula: C₂₂H₃₈O₅ Molecular mass: 382.534 g/mol PubChem compound: 5282381
Misoprostol is an analogue of naturally occurring prostaglandin E1 which promotes peptic ulcer healing and symptomatic relief.
Misoprostol protects the gastroduodenal mucosa by inhibiting basal, stimulated and nocturnal acid secretion and by reducing the volume of gastric secretions, the proteolytic activity of the gastric fluid, and increasing bicarbonate and mucus secretion.
Prostaglandins of the F and E series have been shown to increase collagenase activity in rabbit uterine cervix fibroblasts in vitro and to cause cervical ripening and uterine contraction in vivo. These pharmacodynamic effects are considered to be the mechanism of action relevant for the clinical effect of misoprostol vaginal delivery system.
PGE analogues also have a number of other effects, e.g. relaxation of bronchial and tracheal muscles, increase of mucus secretion and decrease of acid and pepsin secretion in the stomach, increase of renal blood flow, increase of circulating concentrations of adrenocorticotropic hormone and prolactin. These pharmacodynamic effects are considered to be of no clinical importance with the short treatment.
Misoprostol (a synthetic analogue of prostaglandin E1) is used in combination with mifepristone for the termination of pregnancies of ≤49 days of amenorrhea.
In the event of an early termination of pregnancy, the combination of mifepristone-misoprostol leads to an increase in the success rate to about 95% of the cases and accelerates the expulsion of the conceptus. The success rate is around 95% when 600 mg mifepristone is combined with misoprostol 400 microgram orally up to 49 days of amenorrhea.
At the recommended dosage, misoprostol induces contractions of smooth muscle fibres of the myometrium and a relaxation of the cervix uteri. The uterotonic properties of misoprostol should facilitate the opening of the cervix uteri and the expulsion of intra-uterine remains.
At the recommended dosage, misoprostol should not involve cardiac, hepatic or renal undesirable effects.
Misoprostol is rapidly absorbed following oral administration, with peak plasma levels of the active metabolite (misoprostol acid) occurring after about 30 minutes. The plasma elimination half-life of misoprostol acid is 20-40 minutes.
The free acid of misoprostol is less than 90% bound to plasma proteins. Misoprostol is metabolised by fatty acids-oxidising systems, present in several organs of the human body.
After oral administration of 3H-misoprostol approximately 73% of the radioactivity is excreted in urine and approximately 15% in the faeces. Approximately 56% of total radioactivity is eliminated within 8 hours via urine.
Administration of misoprostol with food does not change the bioavailability of misoprostol acid, but reduces the maximum plasma concentration due to a slower absorption rate.
Misoprostol, an ester, is rapidly metabolised to its active metabolite misoprostol acid. Only misoprostol acid is detectable in plasma. The acid is further metabolised to inactive dinor and tetranor acid metabolites prior to excretion in the urine.
In non-pregnant women, the misoprostol vaginal delivery system has a controlled mean in vivo release rate of approximately 7 micrograms/hour over a period of 24 hours. In a study of 24 pregnant women at term gestation, a median Cmax of 45.8 pg/mL with a median Tmax of 4 hours was observed. Median terminal half-life (after removal of the insert) was approximately 40 minutes.
The serum protein binding of misoprostol acid is less than 90% and concentration independent at therapeutic doses.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential.
At high repeated doses in rats and rabbits, misoprostol was foeto- and embryotoxic. No teratogenic potential was observed.
In single- and repeat-dose studies in dogs, rats and mice at multiples of the human dose, toxicological findings were consistent with the known pharmacological effects of the E-type prostaglandins, the main symptoms being diarrhoea, vomiting, mydriasis, tremors and hyperpyrexia.
Intra-uterine but not the intragastric delivery of misoprostol to rats significantly worsened mortality from Clostridium sordellii uterine infection, and impaired bacterial clearance in vivo.
Misoprostol has been shown to alter calcium homeostasis in neuro-2a cells and contribute to abnormal cell function in vitro. Imbalances in calcium homeostasis can potentially affect early neuronal development.
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