estrogen blockers

Some interesting stuff concerning SERM elimination/half life.

''clomiphene citrate is excreted principally through the
intestines. Five days after oral administration, 51% has
been excreted; however, some clomiphene continues to be
excreted for at least 6 weeks (Mikkelson et al., 1986).''

Taken from
Human Reproduction Update 1996, Vol. 2, No. 6 pp. 483–506 _ European Society for Human Reproduction and Embryology
Development, pharmacology and clinical
experience with clomiphene citrate
Richard P.Dickey and Dorsey E.Holtkamp

So if they test you’re gonna be busted for up to 6 weeks.

Does anyone have access to the journal below?? The abstract doesn’t have any figures in it.

Detection of tamoxifen Metabolites by GC–MSD
Authors: H. Báez1; C. Camargo1; H. Osorio1; F. Umpiérrez2
Source: Journal of Chromatographic Science, Volume 42, Number 10, November/December 2004 , pp. 551-553(3)

Clin Pharmacokinet. 2003;42(4):361-72. Links
Pharmacokinetics of selective estrogen receptor modulators.
Morello KC, Wurz GT, DeGregorio MW.
Department of Internal Medicine, University of California, Davis, Sacramento, California 95817, USA.
Selective estrogen receptor modulators (SERMs) are a class of compounds used to treat and prevent breast cancer and osteoporosis. SERMs currently approved for use in patients include tamoxifen, toremifene and raloxifene. These compounds are well tolerated in patients, and the most common adverse effects experienced in patients undergoing SERM therapy include vasomotor symptoms such as hot flashes and vaginal discharge. New SERMs currently under development for use in the treatment and prevention of osteoporosis and breast cancer include ospemifene, a derivative of toremifene, and arzoxifene, a compound very similar in structure to raloxifene. SERMs are administered orally at doses ranging from 20 to 60 mg/day. tamoxifen and toremifene have a bioavailability of approximately 100%, whereas that of raloxifene is only 2%. SERMs are very highly bound to plasma proteins (>95%). tamoxifen and toremifene are metabolised by the cytochrome p450 enzyme system, and raloxifene is metabolised by glucuronide conjugation.

The terminal elimination half-lives of these drugs range from 27.7 hours to 7 days.

The pharmacokinetics of these compounds are affected in hepatically impaired patients, but not in renally impaired patients. SERMs have several potential drug interactions with other agents, such as warfarin, rifampicin (rifampin), cholestyramine and aromatase inhibitors.

So I’m guessing we want the elimination ½ life of 27.7 hours not 7 days! A lot shorter time to get busted in, any ideas which that might be?

Eur J Clin Pharmacol. 2000 Sep;56(6-7):469-75.

Pharmacokinetics of (deaminohydroxy)toremifene in humans: a new, selective estrogen-receptor modulator.

DeGregorio MW, Wurz GT, Taras TL, Erkkola RU, Halonen KH, Huupponen RK.

Department of Internal Medicine, Cancer Center, University of California, Davis, Sacramento 95817, USA. [email protected]

PURPOSE: New selective estrogen-receptor modulators for the treatment and prevention of osteoporosis, cardiovascular disease and breast cancer are currently the focus of intense research. (Deaminohydroxy)toremifene (Z-2-[4-(4-chloro- 1,2-diphenyl-but-1-enyl)phenoxy]ethanol; FC-1271a) has been shown to prevent bone resorption in rats while having no or weak estrogen-like effects on the uterus, which makes it a good candidate drug for osteoporosis prevention. Our purpose here was to examine the pharmacokinetics of (deaminohydroxy)toremifene in humans included in two phase-I studies. METHODS: The first was a single-dose, dose-escalation study with 28 healthy male volunteers. Doses ranged from 10 mg to 800 mg. The second study was conducted during a 12-week period with 40 healthy, post-menopausal women, who received repeated oral doses of 25-200 mg. Standard pharmacokinetic parameters were assessed. RESULTS: In the single-dose study, time to reach peak concentration (tmax) ranged from 1.3 h to 4.0 h; peak concentration (Cmax) ranged from 15 ng/ml to 445 ng/ ml; and

the estimated terminal elimination half-life (mean +/- SD; t1/2) was 24.8 +/- 7.0 h.

In the repeated-dose study, tmax ranged from 1.9 h to 2.6 h at 6 weeks and from 2.5 h to 2.9 h at 12 weeks. Cmax ranged from 295 ng/ml to 1,043 ng/ml at 6 weeks and from 25 ng/ml to 1211 ng/ml at 12 weeks.

The average t1/2 at all dose levels was 29.7 +/- 1.5 h (overall mean +/- SD).

Strong linear correlations between the dose and Cmax and between the dose and the area under the curve were observed in both studies. CONCLUSION: Our results indicate that (deaminohydroxy)toremifene has pharmacokinetics suitable for single daily dosing. The prophylactic use of this agent in women susceptible to development of osteoporosis, cardiovascular disease and breast cancer could, therefore, be tested using a once-daily dosing schedule similar to those of other hormone-replacement therapy regimens.

Looks like Toremifene is on the low end of the ½ life scale, I’m guessing this makes it a better choice than nolva/clomid for athletic use.

(I cant seem to get bolded text so have tried to seperate the bits that seem important)