Metabolic conversion of cyoctol during skin passage in humans.
Upon application of 14C-labeled cyoctol to the forearm of healthy volunteers, no parent cyoctol was detectable in ipsilateral blood plasma. The 14C activity was largely accounted for by a component with higher lipophilicity than the parent compound, as justified from their HPLC retention. Thus, this study suggests that human skin is capable of nearly complete cutaneous first-pass metabolism, resulting in negligible systemic availability of cyoctol. In a comparable experiment, rabbits were also able to convert cyoctol during skin absorption to a more lipophilic metabolite, which was identified as the palmitoleic acid ester of O-demethylated cyoctol by GC/MS. However, chromatographic evidence indicates that the human ipsilateral metabolite differs from the rabbit cyoctol metabolite.
de Zeeuw
R A
RA
Groningen Centre for Drug Research, Bioanalysis and Toxicology Group, University of Groningen, The Netherlands.
Herder
R E
RE
Wiechers
J W
JW
Drenth
B F
BF
D000726:Androgen Antagonists / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001711:Biotransformation; D001643:Bridged Bicyclo Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D007659:Ketones; D011817:Rabbits; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption
D000726:Androgen Antagonists; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D007659:Ketones; C046699:cioteronel