Progesterone preparation

Progesterone is rapidly absorbed following administration by any route. Its half-life in the plasma is approximately 5 minutes, and small amounts are stored temporarily in body fat. It is almost completely metabolized in one passage through the liver, and for that reason it is quite ineffective when the usual formulation is administered orally. However, high-dose oral micronized progesterone preparations have been developed that provide adequate progestational effect. 

Ingber A, Trattner A, David M. Hypersensitivity to an oestrogen-progesterone preparation and possible relationship to autoimmune progesterone dermatitis and corticosteroid hypersensitivity. J Dermatol Treat 1999 10 139 10. 

Progestagens Corpus luteum Progesterone Prepares uterine lining for egg implantation maintenance of pregnancy... 

Progestogens such as progesterone are synthesized in the corpus luteum, and their secretion is stimulated by LH. As mentioned, in concert with estradiol, progesterone prepares the uterine endometrium for implantation of the fertilized ovum and acts as a differentiation factor in mammary gland development. 

Megestrol acetate (79) is stmcturaHy related to progesterone (1). It has been prepared from medroxyprogesterone acetate (74) by chloranil-mediated dehydrogenation. It also has been prepared from hydroxyprogesterone acetate (42) via 6-methylenation and double-bond migration (109,110). 

However, treatment of cortisone 3,20-bissemicarbazone with acetic anhydride and pyridine removes the 20-semicarbazone group preferentially. Selective removal of a protecting group can be also achieved by a selective reaction to give a new intermediate which can be converted into the desired product ketone. Thus progesterone 20-monoenol acetate (42) is prepared from the 3,20-bisenol acetate (40) via selective electrophilic attack of iodine at C-6 followed by reductive dehalogenation of (41). ... 

Preparation of Ba-Methyi-17-Hydroxy progesterone 17-Acetate 1 g of 6a-methyl-17a-hy-droxyprogesterone was dissolved in a mixture of 10 ml of acetic acid and 2 ml of acetic anhydride by heating. After solution was effected the mixture was cooled to 15°C, and 0.3 g of p-toluenesulfonic acid was added. After allowing the mixture to stand for a period of 2 /a hours at room temperature, the pink solution was poured into ice water to give an amorphous solid which was recovered by filtration. 

Preparation of 11-Keto-6 -Methy progesterone 3,20-Bis-(Ethylene Ketal) A mixture of 5 g of 11-keto-6(3-methylprogesterone (Spero et al, 7. Am. them. Soc., 78, 6213 (1956)], 503 ml of benzene, 26 ml of ethylene glycol, and 0.152 g of p-toluenesulfonic acid monohydrate was stirred and heated under reflux for 22 hours while water was removed by means of a water trap. The reaction mixture was then cooled to 30°C, 0.4 ml of pyridine was added, and stirring was continued for 10 minutes. 

These discoveries generated a lot of effort over the successive 25 years in the preparation of especially designed drug delivery systems for the controlled release of radioactive progesterone [654], colchicine [656], naproxen [657,673, 674], mitomycin C [675-677], inulin [678], trimethoprin [657], succinylsul-fathiazole [657], ethacrynic acid [653], and steroids [633], regardless of whether these drugs are physically trapped in polyphosphazene matrices, or chemically bonded to the polymer skeleton. 

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