Mifepristone: bioavailability, pharmacokinetics and use-effectiveness

摘要: The potentiality of mifepristone as an abortifacient and contraceptive drug along with its pharmacokinetic parameters is reviewed. Mifepristone or RU486 acts antagonist to progestational glucocorticoid functions. It orally active compound nearly 70% absorption rate but bioavailability reduced around 40% because the first-pass effect. Peak plasma concentrations 1.9 +/- 0.8, 3.8 0.9 5.3 1.3 micromol/l are reached within 1-2 h after oral administration 50, 200 600 mg in women, respectively, maintained at relatively high level up 48 72 depending on ingested dose. kinetics followed two-compartment open model a mean alpha-half-life 1.4h, volume distribution 1.47 l/kg beta-half-life 20-30 most subjects studied. Clearance from body was mainly through feces (83%). Biologically mono-demethylated, di-demethylated hydroxylated metabolites were found soon mifepristone. mono-demethylated metabolite bind progesterone receptors affinity. Mifepristone-bound receptor dimers suppress transcription activation thus, bring about anti-progestational activity that makes potential agent. Clinical trials for termination early pregnancy 50-600 plus prostaglandin analogue achieved success 82-97%. However, abdominal pain, cramping, nausea, vomiting, bleeding delay onset next menstrual cycle side effects. Administration 25 twice 12h apart, post-coital showed 100% efficacy. A low dose which does not inhibit ovulation fertility significantly by affecting endometrial milieu. These findings suggest dose(s) mifepristone, less, may be used combination vaginal misoprostol efficacy minimal no