Английская Википедия:Estradiol stearate
Шаблон:Short description Шаблон:Drugbox
Estradiol stearate (E2-17-St), also known as estradiol octadecanoate and sold under the brand name Depofollan, is a naturally occurring estrogen and an estrogen ester – specifically, the C17β stearate ester of estradiol.[1][2][3][4][5] It occurs in the body as a very long-lasting metabolite and prohormone of estradiol.[5] The compound is one of the components that collectively constitute lipoidal estradiol, another of which is estradiol palmitate.[6][5] It is extremely lipophilic and hydrophobic.[5] Estradiol stearate has no affinity for the estrogen receptor, requiring transformation into estradiol via esterases for its estrogenic activity.[7][8][9][5] The compound does not bind to sex hormone-binding globulin or α-fetoprotein, instead being transported by lipoproteins such as high-density lipoprotein and low-density lipoprotein.[5]
Estradiol stearate has a prolonged duration of action relative to estradiol regardless of whether it is given by intravenous injection or subcutaneous injection.[7] This is in contrast to short-chain fatty acid esters of estradiol, such as estradiol benzoate, which do not show a prolonged duration with intravenous injection.[10] When administered by intravenous injection in rodents, estradiol stearate has a greatly increased terminal half-life relative to estradiol (6 hours vs. 2 minutes).[7] Estradiol stearate also had a half-life that was 60% longer than that of estradiol arachidonate, despite similar ester chain lengths.[7] In contrast to the long-chain esters, the half-lives of short-chain estradiol esters such as estradiol acetate and estradiol hexanoate were the same as that of estradiol.[7] As such, whereas short-chain estradiol esters are rapidly hydrolyzed, long-chain estradiol esters like estradiol stearate are resistant to metabolism.[7] Thus, the prolongation of effect of short-chain estradiol esters is purely due to their increased lipophilicity and slow release from the injected depot, whereas the prolonged duration of long-chain estradiol esters is due both to this property and to their resistance to metabolism.[7] Estradiol stearate is susceptible to first-pass metabolism in the liver, and hence has much greater potency by subcutaneous injection than by oral administration.[7]
In addition to its endogenous role, estradiol stearate was previously available as a pharmaceutical drug for use via depot intramuscular injection.[1][2] The medication was introduced between 1938 and 1941 under the brand name Depofollan.[11][12] It has been used to treat prostate cancer.[13][14] Estradiol stearate is a long-acting estrogen[15][12] and is said to have been the first long-acting estrogen used in medicine, although it was never widely employed.[12] It was reported to have a duration of more than one month.[12] The medication was provided as an oil solution in ampoules containing 15 mg estradiol stearate.[15][14] It was manufactured by Chinoin, a Hungarian pharmaceutical company.[15][14][11][16] The compound was studied by Karl Miescher in 1938[17] and was patented by Miescher and Chinoin in 1939 and 1941, respectively.[18][19] A similar clinically used long-acting estradiol ester is estradiol undecylate, which has 11 carbon atoms instead of the 18 carbon atoms in estradiol stearate.[1][2]
Шаблон:Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors
Шаблон:Structural properties of selected estradiol esters
See also
References
Шаблон:Estradiol Шаблон:Estrogens and antiestrogens Шаблон:Estrogen receptor modulators
Шаблон:Genito-urinary-drug-stub Шаблон:Steroid-stub
- ↑ 1,0 1,1 1,2 Шаблон:Cite book
- ↑ 2,0 2,1 2,2 Шаблон:Cite book
- ↑ Шаблон:Cite book
- ↑ Шаблон:Cite book
- ↑ 5,0 5,1 5,2 5,3 5,4 5,5 Шаблон:Cite journal
- ↑ Шаблон:Cite book
- ↑ 7,0 7,1 7,2 7,3 7,4 7,5 7,6 7,7 Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- ↑ 11,0 11,1 Шаблон:Cite book
- ↑ 12,0 12,1 12,2 12,3 Шаблон:Cite book
- ↑ Шаблон:Cite journal
- ↑ 14,0 14,1 14,2 Шаблон:Cite book
- ↑ 15,0 15,1 15,2 Шаблон:Cite book
- ↑ Шаблон:Cite book
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite patent
- ↑ Шаблон:Cite patent
