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.