The metabolism of acitretin and isoacitretin in the in situ isolated perfused rat liver.
1. The metabolism of acitretin and its 13-cis isomer, isoacitretin, has been investigated in the in situ isolated perfused rat liver in order to differentiate the action of the liver from that of the gut on the metabolism of these isomers. 2. Acitretin undergoes alpha-oxidation, chain shortening O-demethylation, and glucuronidation in the perfused rat liver. 3. Isoacitretin undergoes glucuronidation as the major, almost exclusive, route of metabolism in the perfused rat liver. 4. The difference in the hepatic metabolism of the cis and trans isomers of this retinoid may explain the differences in their pharmacokinetics, and may help in understanding the pharmacokinetics of related retinoids.
Cotler
S
S
Department of Drug Metabolism, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
Chang
D
D
Henderson
L
L
Garland
W
W
Town
C
C
D017255:Acitretin / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003640:Dealkylation; D005965:Glucuronates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D005965:Glucuronates; D017255:Acitretin