CONVERSION OF FLOSEQUINAN TO THE SULFONE METABOLITE IN SUBCELLULAR-FRACTIONS OF HUMAN LIVER, IN-VITRO

Flosequinan was metabolized in a NADPH-dependent reaction, by S-oxidat ion to its principal metabolite, the sulphone. Most of the sulphone me tabolite was formed within 20 min and reached a plateau by 60 min, fol lowing incubations of flosequinan (31, 61 or 122 muM) with the microso mal fraction. Flosequinan was metabolized mainly by the microsomal fra ction. The S-oxidation of flosequinan in incubations containing mitoch ondrial and cytosolic fractions was 13 and 5%, respectively, of that d etected in the microsomal fraction. The route of metabolism of flosequ inan in-vitro correlates closely with that previously observed in-vivo . This model could be useful for studying the potential effects of oth er drugs on flosequinan metabolism in-vitro.