Linked Life Data

6158464

Source:http://linkedlifedata.com/resource/pubmed/id/6158464

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1980-12-18
pubmed:abstractText
The metabolic fate and distribution of the anti-androgenic agent, 17 alpha-acetoxy-6-chloropregna-4, 6-diene-3, 20-dione (chlormadinone acetate, CMA), was investigated using guinea-pigs and rats. In order to elucidate the metabolic outcome, chlormadinone acetate was labelled with 3H at position C-1 and with deuterium at methyl moiety of the 17alpha-acetate. Guineapigs were maintained for 7 days on a diet containing 1% chlormadinone acetate having a ratio of d2/d0=1 and then for 1 day on a diet containing 1% chlormadinone acetate having radioactivity. The isolation and purification of the urinary and fecal metabolites were usually carried out in the manner shown in Fig. 1 and 2. The metabolites identified were as follows: the parent drug, monohydroxychlormadinone acetate having the additional hydroxy function in the steroid skeleton, 15 beta-hydroxy, 2 alpha-, 2 beta-hydroxy and unknown position, dihydroxy chlormadinone acetate, 2 alpha-, 3 beta-dihydroxy, 2 alpha-, 3 alpha-dihydroxychlormadinone acetate. Further, three dechlornated and reduced metabolites were also isolated from urine and feces. These were 17 a-acetoxy-5a-pregnane-3 beta-ol-20-one and its isomer, and 17-acetoxy-5 beta-pregnane-2 beta, 3 beta, 15a-triol-20-one. But 3 beta-hydroxychlormadinone acetate possessd with anti-androgenic activity, one of the main metabolites in humans and rats, was not found in the excreta of the guinea-pigs. However, the main metabolite on the prostate of the guinea-pigs and rats and 3 beta-hydroxychlormadinone acetate. Chlormadinone acetate causes regression of the seminal vesicle and prostate in oral administration to a mammalian. It was therefore hypothesized that chlormadinone acetate might inhibit the uptake and retention of testosterone in these tissues. To elucidate this hypothesis, the accumulation of testosterone-3H and chlormadinone acetate-3H in several organs was determined on castrated rats and normal rats, respectively. When 1.0 muM of testosterone-3H was given to the castrated rats, a maximal accumulation of radioactivity resulted in seminal vesicle and prostate at 15 approximately 120 min. While the treatment of chlormadinone acetate significantly prevented the accumulation of testosterone-3H in the seminal vesicle and prostate, but levels in fat and muscle were not evident. In addition, to prove the accumulation of chlormadinone acetate in androgen target tissues, 3 muM of chlormadinone acetate-3H was similarly administered to castrated rats. The uptake of chlormadinone acetate on the target organs was higher than that in normal rats at 5 approximately 30 min.
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0029-0661
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1116-29
pubmed:dateRevised
2011-7-27
pubmed:meshHeading
pubmed:year
1980
pubmed:articleTitle
[The in vivo metabolism of chlormadinone acetate in guinea pig and the uptake of testosterone-3 H and chlormadinone acetate-3 H in prostate of castrated male rat (author's transl)].
pubmed:publicationType
Journal Article, English Abstract