Premarin Pharmacology, Pharmacokinetics, Studies, Metabolism - Estrogens Conjugated

Premarin Pharmacology, Pharmacokinetics, Studies, Metabolism - Estrogens Conjugated

CLINICAL PHARMACOLOGY

Estrogens are important in the development and maintenance of the female reproductive system and secondary sex characteristics. They promote growth and development of the vagina, uterus, and fallopian tubes, and enlargement of the breasts. Indirectly, they contribute to the shaping of the skeleton, maintenance of tone and elasticity of urogenital structures, changes in the epiphyses of the long bones that allow for the pubertal growth spurt and its termination, growth of axillary and pubic hair, and pigmentation of the nipples and genitals. Decline of estrogenic activity at the end of the menstrual cycle can bring on menstruation, although the cessation of progesterone secretion is the most important factor in the mature ovulatory cycle. However, in the preovulatory or nonovulatory cycle, estrogen is the primary determinant in the onset of menstruation. Estrogens also affect the release of pituitary gonadotropins.

The pharmacologic effects of conjugated estrogens are similar to those of endogenous estrogens. The tablets are soluble in water and are well absorbed from the gastrointestinal tract. The injection is soluble in water and may be administered by intravenous or intramuscular injection. The cream is soluble in water and may be absorbed from mucosal surfaces after local administration.

In responsive tissues (female genital organs, breasts, hypothalamus, pituitary) estrogens enter the cell and are transported into the nucleus. As a result of estrogen action, specific RNA and protein synthesis occurs.

Metabolism and inactivation occur primarily in the liver. Some estrogens are excreted into the bile; however, they are reabsorbed from the intestine and returned to the liver through the portal venous system. Water-soluble estrogen conjugates are strongly acidic and, therefore, ionized in body fluids, which favor excretion through the kidneys since tubular reabsorption is minimal.