Clinical evidence that acitretin is esterified to etretinate when administered with ethanol
- Hoffmann-LaRoche Inc., Nutley, NJ (United States)
A previously unexpected metabolic pathway, ethyl esterification of acitretin (A) to etretinate (E), was studied in 10 healthy subjects. Subjects received single 100 mg oral doses of A with a standard meal alone or with concomitant ethanol ingestion in a 2-way randomized crossover design. Ethanol was ingested over a 3-hour period. Blood samples were collected up to 48 hours after A administration. Plasma concentrations of E,A and 13-cis A were determined by a specific HPLC assay. Blood ethanol concentrations were also determined E plasma concentrations were observed in all subjects following A and ethanol intake. The mean peak E concentration was 59 ng/ml, with E concentrations generally dependent on ethanol concentrations. E concentrations were not detectable during treatment with A alone. In conclusion, ethyl esterification of A to E occurs when A is given with ethanol. Both A and E are teratogenic, but differ in elimination half-life; 2 days (A) vs 120 days (E), a profound pharmacokinetic difference.
- OSTI ID:
- 7049951
- Report Number(s):
- CONF-9204141-; CODEN: FAJOE
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 6:4; Conference: Federation of American Societies for Experimental Biology (FASEB) meeting, Anaheim, CA (United States), 5-9 Apr 1992; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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560300* - Chemicals Metabolism & Toxicology