DISPOSITION OF [C-14] ACITRETIN IN HUMANS FOLLOWING ORAL-ADMINISTRATION

The disposition of the antipsoriatic agent, acitretin, was investigate d in six healthy human volunteers who each received a single, oral 50 mg dose of [C-14]acitretin (50 mu Ci). plasma, urine, and feces were c ollected for 240 hr after administration. Mean values of 20.9 and 62.6 % of the administered dose were recovered in the urine and feces, resp ectively. The terminal elimination half-life of total radioactivity fr om the plasma was similar to 120 hr. Extraction of pooled plasma sampl es followed by separation by HPLC and quantitation by liquid scintilla tion counting indicated that acitretin and its 13-cis-isomer, isoacitr etin, were minor fractions of the total drug-related material in the p lasma at most time points up to 72-hr postdose. The structures of acit retin, isoacitretin, and two other ,3,6-trimethylphenyl)-2,6-dimethyl- 5,7-octadienoic acid (I) and 4-hydroxy-2,3,6-trimethylphenyl)-2,6-dime thyl-5,7- octadienoic acid (II)-were confirmed by MS and cochromatogra phy with authentic standards. I and II were major fractions of the dru g-related material in the plasma at all time points. Other compounds, whose structures could not be confirmed, also account for a significan t fraction of the circulating radioactivity.