Pharmacokinetics of 14C-etretinate in healthy volunteers and two patients with biliary T-tube drainage.
The pharmacokinetic profile of 14C-etretinate, a retinoid that is effective in the treatment of psoriasis, was studied in six healthy male volunteers and two biliary T-tube patients. Following a 100 mg oral dose of 14C-etretinate (20 microcurie), etretinate and its major blood metabolites (etretin, isoetretin) were measured by HPLC and total carbon-14 was measured in blood, bile, urine, and feces by liquid scintillation counting. Etretinate was extensively metabolized in healthy volunteers and in T-tube patients. During the absorption phase, 75 per cent of the total radioactivity in the blood could be accounted for as etretinate, etretin, and isoetretin whereas these compounds accounted for only approximately 12 per cent of the blood radioactivity in T-tube patients over the same time period. The blood concentrations of etretinate, etretin, and isoetretin appeared to be substantially reduced in T-tube patients compared to those in healthy volunteers. A higher proportion of the total drug was excreted in the feces and bile of the T-tube patients (84 per cent) than in the feces of healthy volunteers (62 per cent). The major factor responsible for the observed decrease in etretinate blood concentrations following biliary cannulation appears to be the reduced absorption of etretinate due to the elimination of solubilizing bile salts in the duodenum. Carbon-14 related material was detected in urine and feces for as long as 3 weeks in healthy subjects supporting the previous observation that a long terminal elimination half-life exists for etretinate, even following a single dose of the compound.
Lucek
R W
RW
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ.
Dickerson
J
J
Carter
D E
DE
Bugge
C J
CJ
Crews
T
T
Vane
F M
FM
Cunningham
W
W
Colburn
W A
WA
D001646:Bile / Q000032:analysis*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005050:Etretinate / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011865:Radioisotope Dilution Technique; D012016:Reference Values
D002250:Carbon Radioisotopes; D005050:Etretinate