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Hair Loss Study Abstract: Preliminary pharmacokinetics and metabolism of novel non-steroidal antiandrogens in
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Title
Preliminary pharmacokinetics and metabolism of novel non-steroidal antiandrogens in the
rat: relation of their systemic activity to the formation of a common metabolite.
Author
Cousty-Berlin D, Bergaud B, Bruyant MC, Battmann T, Branche C, Philibert D
Address
Centre de Recherches Roussel Uclaf, Romainville, France.
Source
J Steroid Biochem Mol Biol, 51: 1-2, 1994 Oct, 47-55
Abstract
The non-steroidal antiandrogens, RU 58841 and RU 56187 are amongst the most active of a
new series of N-substituted aryl hydantoins or thiohydantoins. Their pharmacokinetics and
principal metabolic profiles have been evaluated in rat plasma after intravenous
administration of a 10 mg/kg dose. Both compounds disappear relatively rapidly from the
plasma (elimination half-life of the order of 1 h), but they form a common metabolite, the
N-desalkyl derivative, RU 56279, which is eliminated much more slowly. The percentage
transformations of each into RU 56279, estimated from the AUCs of the metabolite compared
with the AUC obtained after administration of RU 56279 itself, were respectively 1% and
77%. In parallel, their in vivo activity, as well as that of their metabolites, was
determined with respect to parameters related to systemic antiandrogenic effects (prostate
and seminal vesicle weights). The results showed that: (1) the common metabolite, RU
56279, is clearly antiandrogenic; (2) there appears to be a relationship between the
percentage formation of this metabolite and the systemic antiandrogenic activity of the
compounds. Thus, the pharmacological profile of RU 58841 which displays a potent local
antiandrogenic activity without systemic effects can be related to its very low propensity
to form the N-desalkyl metabolite.
Language of Publication
English
Unique Identifier
95034339
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