Byt. Perotti et al., HPLC ASSAY FOR FK-506 AND 2 METABOLITES IN ISOLATED RAT HEPATOCYTES AND RAT-LIVER MICROSOMES, Pharmaceutical research, 11(6), 1994, pp. 844-847
Despite the current use of a standard two-step enzyme immunoassay in t
he clinical monitoring of the immunosuppressant FK 506, the lack of sp
ecificity for the parent drug in this assay renders it unsuitable for
drug metabolism studies. An HPLC assay has been developed for studying
the metabolism of FK 506 in isolated hepatocytes and microsomal mixtu
res. This assay allows simultaneous measurement of the parent drug and
two of its time dependent metabolites. Metabolism of this drug was st
udied in intact rat liver cells and rat liver microsomes. We have show
n that the metabolites observed are products of phase 1 oxidation reac
tions. Correlation of the 6 beta-testosterone hydroxylase activity wit
h the FK 506 metabolite (Mi) initial formation rate is consistent with
the belief that CYP 3A isozymes are involved in FK 506 metabolism in
male rats.