The effect of repeat administration of GTS-21 on hepatic microsomal enzymes
was determined in rats administered the drug at levels of 3, 60 and 300 mg
/kg/day for 7 days. Liver weight and cytochrome P450 (CYP) contents were no
t changed. Cytochrome b(5) contents were increased at the mid and high dose
s of GTS-21, as the contents increased with increasing dose, but were uncha
nged at the low dose. Five selective activities of CYP isoforms, acetanilid
e hydroxylase (CYP1A2), tolbutamide hydroxylase (CYP2C6), dextromethorphan
O-demethylase (CYP2D1), p-nitrophenol hydroxylase (CYP2E1) and erythromycin
N-demethylase (CYP3A) were examined. Enzyme activities were changed only a
t the highest dose; the activity of CYP1A2 was increased by 71% and the act
ivities of CYP2C6 and CYP2D1 were decreased by 37 and 19%, respectively. At
low and mid doses of GTS-21, all activities were unchanged. These data ind
icate that GTS-21 is not a strong modulator of the mixed-function oxidase s
ystem. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.