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DESCRIPTION

Mifepristone

Mifepristone is a drug that blocks a hormone called progesterone that is needed for pregnancy to continue. Mifepristone, when used together with another medicine called misoprostol, is used to end an early pregnancy. the chemical name for Mifepristone is 11b-[p-(Dimethylamino) pheny]-17b-hydroxy-17-(1-propy-nyl) estra-4,9-dien-3one. its molecular formula is c h no and structural formula is 429.59.

Misoprostol:

Misoprostol is used in combination with another drug mifepristone to end a pregnancy.

The chemical name for Misoprostol is Mixture of methyl 7-[(1RS, 2RS, 3RS)-3-hydroxy-2-[(1E, 4RS)-4-methoxloct-1-enyl] heptanoate and methyl its Molecular formula is C H O structure formula is 382.5

CLINICAL PHARMACOLOGY:

Pharmacodynamics:

Mifepristone

Pharmacotherapeutic group: other sex hormone and modulator of the genital system/Antiprogestogen, ATC code G03 V B01.

The anti-progestational activity of Mifepristone results from competitive interaction with progesterone of progesterone -receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone and the termination of pregnancy result. Doses of 1mg/kg or greater of Mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction -induced activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity.

Mifepristone induces softening and dilatation of the cervix, softening and dilatation has been shown to be detectable from 24 hours after administration of Mifepristone and increases to a maximum at approximately 36 – 48 hours after administration.

Glucocorticoid bioactivity (GBA) may be depressed for several days following a single administration of 200mg mifepristone for termination of pregnancy. The clinical implications of this are unclear, however vomiting and nausea may be increased in susceptible women. in animals at doses of 10 to 25 mg/kg it inhibits the action of dexamethasone.

Doses of 4.5mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol. The maximum effect is achieved when prostaglandin was administered 36 to 48 hours after mifepristone.

Misoprostol

Pharmacotherapeutic group Oxytocics/Prostaglandins, ATC code: G02AD06.

Prostaglandin E1causes myometrial countractions by interacting with specific receptors on myometrial cells. this interaction results a change in calcium concentration, thereby initiating muscle contraction. By interacting with prostaglanding receptors, Misoprostol causes the cervix to soften and the uterus to contract, resulting in the expulsion of the uterine contents.

in the event of an early termination of pregnancy, the combination of a prostaglandin analogue used in a sequential regimen after mifepristone leads to the expulsion of the conceptus

PHARMACOKINETICS:

Mifepristone

following oral administration of a signal dose of 600 mg, Mifepristone is rapidly absorbed, with a peak plasma concentration of 1.98 mg/l occurring approximately 90 minutes after ingestion. The absolute bioavailability of a 20 mg oral dose is 69%.

Mifepristone is 98% bound to plasma proteins, albumin and alpha 1-acid glycoprotein. Binding to the latter protein is saturable, and the drug displays nonlinear kinetics with respect to plasma concentration and clearance, Following a distribution phase, elimination of Mifepristone is slow at first (50 % eliminated between 12 and 72 hours ) and then becomes more rapid with a terminal elimination half-life of 18 hours.

Metabolism of mifepristone is primary via pathways involving N-demethylation and terminal hydroxylation of the 17-proynyl chain in vitro studies have shown that CYP4503A34 is primarily responsible for the metabolism. the three major metabolites identified i humans are:(1) RU 42 633, MOST WIDELY found in plasma, is the N-monodemethylated metabolite; (2) RU 42 848, which results from the loss of two methyl groups from the 4-dimethylaminophenyl in position 11b: and (3) RU 42 698, which results from terminal hydroxylation of the 17-propynyl chain.

Mifepristone is mainly excreted in faeces. After administration of a 600mg labelled dose, 10% of the total radioactivity is eliminated in the urine 90% in the faeces.