A potentially new metabolic pathway: ethyl esterification of acitretin.
1. The acidic retinoid, acitretin, was esterified to etretinate (ethyl ester) by rat and human liver 12,000 g supernatant. The amount of etretinate formed was increased by adding ethanol to the rat preparation. 2. This esterification almost certainly involves enzymic catalysis, and the amounts of etretinate formed were increased by the use of fresh rat liver. 3. Co-administration of acitretin and ethanol to rats resulted in a maximum plasma concentration of etretinate at approximately 1 h after dosing. Secondary maxima were induced by administering ethanol alone at 5 and 8 h after dosing with acitretin. 4. Comparison of acitretin and etretinate concentrations in rat portal and jugular vein plasma after ethanol administration indicated that the ester was formed mainly systematically, rather than during absorption. 5. The results of our study in the rat could indicate that the presence of etretinate in plasma of some patients being treated with acitretin may result from the intake of alcohol.
Chou
R C
RC
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Wyss
R
R
Huselton
C A
CA
Wiegand
U W
UW
D017255:Acitretin / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004951:Esterification; D005050:Etretinate / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051381:Rats
D005050:Etretinate; D017255:Acitretin