What is the half-life of Clomid (clomiphene citrate)?

Half-Life of Clomid (Clomiphene Citrate)

The half-life of clomiphene citrate varies between its isomers, with zuclomiphene (cis) having a significantly longer half-life that allows detectable levels to persist in the body for more than a month after administration. 1

Pharmacokinetic Properties of Clomiphene Citrate

• Clomiphene citrate consists of two isomers: zuclomiphene (cis) and enclomiphene (trans) 1
• Enclomiphene has a shorter half-life of approximately 24 hours 2
• Zuclomiphene has a much longer half-life, with detectable levels persisting for more than a month in the body 1
• Complete elimination of clomiphene from the body typically takes 5-7 half-lives, meaning zuclomiphene may remain in the body for 14-20 days or longer 3

Absorption and Elimination

• Clomiphene citrate is readily absorbed when taken orally 1
• The drug is primarily excreted in feces (approximately 42% of the dose) 1
• Urinary excretion accounts for about 8% of the dose 1
• Cumulative urinary and fecal excretion averages about 50% of an oral dose and 37% of an intravenous dose after 5 days 1
• Some labeled drug (14C) can still be detected in feces up to 6 weeks after administration 1

Clinical Implications of Clomiphene's Long Half-Life

• The prolonged half-life of zuclomiphene suggests possible stereo-specific enterohepatic recycling or sequestering of this isomer 1
• Active drug may remain in the body during early pregnancy in women who conceive during the treatment cycle 1
• When planning pregnancy, the prolonged half-life should be considered to minimize potential fetal exposure during critical developmental periods 3
• The extended presence of the drug creates a longer "window" during which subtherapeutic drug levels persist, which can be clinically significant 3

Pharmacodynamic Properties

• Clomiphene citrate competes with estrogen for estrogen-receptor binding sites 1
• It may delay replenishment of intracellular estrogen receptors 1
• The drug initiates a series of endocrine events that lead to increased pituitary gonadotropin release, stimulating follicular development 1
• Both estrogenic and antiestrogenic properties of clomiphene appear to participate in ovulation induction 1
• The zuclomiphene isomer has greater estrogenic activity than enclomiphene 1

Monitoring Considerations

• Predicting complete elimination from the body is crucial for clinical use, especially when planning pregnancy 3
• The extended half-life should be considered when determining treatment duration and timing of conception attempts 3
• There is no evidence of a "carryover effect," though spontaneous ovulatory menses have been noted in some patients after discontinuation of therapy 1