Conversion of flosequinan to the sulphone metabolite in subcellular fractions of human liver, in-vitro.
Flosequinan was metabolized in a NADPH-dependent reaction, by S-oxidation to its principal metabolite, the sulphone. Most of the sulphone metabolite was formed within 20 min and reached a plateau by 60 min, following incubations of flosequinan (31, 61 or 122 microM) with the microsomal fraction. Flosequinan was metabolized mainly by the microsomal fraction. The S-oxidation of flosequinan in incubations containing mitochondrial and cytosolic fractions was 13 and 5%, respectively, of that detected in the microsomal fraction. The route of metabolism of flosequinan in-vitro correlates closely with that previously observed in-vivo. This model could be useful for studying the potential effects of other drugs on flosequinan metabolism in-vitro.
Kamali
F
F
Department of Pharmacological Sciences, Wolfson Unit of Clinical Pharmacology, The University, Newcastle upon Tyne, UK.
Edwards
C
C
D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D011804:Quinolines / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013450:Sulfones / Q000378:metabolism*; D014665:Vasodilator Agents / Q000378:metabolism*
D011804:Quinolines; D013450:Sulfones; D014665:Vasodilator Agents; D009249:NADP; C047316:flosequinan