Types of clomiphene

Part II ,      

1)What it is? Pharmacokinetics

It is a SERM, Blocks Hypothalamus Clomiphene (Nagori):- Zuclomiphene (cis form) is only 38% in ordinary clomiphene. but zu-CLOM(TRANS FORM 0 IS  62% AND VIRTUALLY .

Q.2. Which isomer to use?  En is more potent and responsible for OI. Besides life time is also short.

It is a raceme mixture of two stereoisomer’s. CLOMID (clomiphene citrate tablets USP) is an orally administered, nonsteroidal, ovulatory stimulant designated chemically as 2-[p-(2-chloro-1,2-diphenylvinyl)phenoxy] triethylamine Citrate (1:1). It has the molecular formula of C26H28ClNO • C6H8O7 and a molecular weight of  598.09. It is represented structurally as: .

CC is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)]

Containing between 30% and 50% of the cis-isomer.

Each white scored tablet contains 50 mg clomiphene citrate USP. The tablet also contains the following inactive ingredients: corn starch, lactose, magnesium stearate, pregelatinized

Cornstarch, and sucrose. a present in the feces 6 weeks after administration. Subsequent single-

dose studies in normal volunteers showed that zuclomiphene (cis) has a longer half-life than

enclomiphene (trans). Detectable levels of zuclomiphene persisted for longer than a month in

these subjects. This may be suggestive of stereo-specific enterohepatic recycling or sequestering

of the zuclomiphene. Thus, it is possible that some active drug may remain in the body during

early pregnancy in women who conceive in the menstrual cycle during CC therapy.

1)HOW CC ACTS? CC is a drug of considerable pharmacologic potency. With careful selection and proper .Management of the patient, CLOMID has been demonstrated to be a useful therapy for the .Anovulatory patient desiring pregnancy.

Clomiphene citrate is capable of interacting with estrogen-receptor-containing tissues, including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. It may compete with estrogen for estrogen-receptor-binding sites and may delay replenishment of intracellular

estrogen receptors. Clomiphene citrate initiates a series of endocrine events culminating in a

preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event in

response to a course of clomiphene therapy is an increase in the release of pituitary

gonadotropins. This initiates steroidogenesis and folliculogenesis, resulting in growth of the

ovarian follicle and an increase in the circulating level of estradiol. Following ovulation, plasma

progesterone and estradiol rise and fall as they would in a normal ovulatory cycle.

Available data suggest that both the estrogenic and antiestrogenic properties of clomiphene may participate in the initiation of ovulation. The two clomiphene isomers have been found to have mixed estrogenic and antiestrogenic effects, which may vary from one species to another. Some

data suggest that zuclomiphene has greater estrogenic activity than enclomiphene. Clomiphene citrate has no apparent progestational, androgenic, or antiandrogenic effects and

does not appear to interfere with pituitary-adrenal or pituitary-thyroid function

Why En- clomiphene is better?

En & Zu clomiphene. En is more potent as OI. Half life is short, But Zu last long in the body as many as 1 month after stimulation. In obese women higher dose –no benefit.

 Q.4. What is the prevalence of CC resistance case & how do we treat that?    About 20-25 % cases do not respond to CC. The options are further investigations & treat with followings:.

 Q.5. Is there any Carry Over Effect?

 Although there is no evidence of a “carryover effect” of CC , spontaneous ovulatory menses have been noted in some patients after CLOMID therapy.

Q.5. what is the pregnancy rates?

CLINICAL STUDIES

During clinical investigations, 7578