Dydrogesterone-progestin and its pharmacology

DESCRIPTION:

 A synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit ovulation.

PHARMACOKINETICS:

1.Metabolism: Dydrogesterone is readily absorbed after oral administration. Metabolized in the liver, the metabolite 20-dihydrodydrogesterone is biologically active, unlike the metabolites of progesterone (pregnanediol, pregnanetriol and pregnanolone) which are inactive. The levels of DHD, which is the main active metabolite, is also found to peak about 1.5 hours post dosing. 

 Half life : Dydrogesterone: 5-7 hours, 20-dihydrodydrogesterone (DHD) metabolite: 14-17 hours.

 Absorption: Rapidly absorbed in the gastrointestinal tract with a bioavailability of 28%.

 2. Elimination: Dydrogesterone and its metabolites are excreted predominantly in urine. Total clearance of plasma is at a rate of 6.4 L/min. Within 72 hours, excretion is virtually complete. DHD is preponderantly present in the urine as a conjugate of glucuronic acid. Approximately 85% of the oral dose is successfully egested from the body within 24 hours. The average terminal half-lives of DHD and dydrogesterone vary between 14–17 and 5–7 hours, respectively.

PHARMACODYNAMICS:

Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis.

SIDE EFFECTS:

Migraine , headache , breastpain/tenderness , menstural disorder , nausea , vomiting , botting or weight gain.

CONTRAINDICATIONS:

 1.Contraindicated in patients with undiagnosed, abnormal vaginal bleeding, blood clot disorder, stroke, incomplete abortion, breast cancer, brain cancer, breastfeeding mothers, liver dysfunction, and hypersensnceitivity.

  2.The drug is contraindicated in children under age 18 years. 

  3.The drug should not be given to pregnant women who are not at any risk of abortion or in patient with advanced pregnancy.

THERAPEUTIC USES:

 1. Dysmenorrhea.

 2. Secondary amenorrhoea.

 3. Dysfunctional uterine bleeding and irregular cycles.

 4. Infertility due to luteal insufficiency.

 5. Miscarriage.

 6. Endometriosis.

 7. Hormone replacement therapy.

REFERENCE:-Tripathi K D"Essential of medical pharmacology",7th edition ,page no-316,318.