The effect of repeat administration of GTS-21 on mixed-function oxidase activities in rat.
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 not changed. Cytochrome b5 contents were increased at the mid and high doses of GTS-21, as the contents increased with increasing dose, but were unchanged at the low dose. Five selective activities of CYP isoforms, acetanilide 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 at the highest dose; the activity of CYP1A2 was increased by 71% and the activities 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 indicate that GTS-21 is not a strong modulator of the mixed-function oxidase system.
Azuma
R
R
Pharmacokinetics Research Laboratory, Taiho Pharmaceutical Co, Ltd, Tokushima, Japan. ryu-azuma@taiho.co.jp
Komuro
M
M
Black
S R
SR
Mathews
J M
JM
D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001597:Benzylidene Compounds / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D015786:Cytochromes b5 / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000187:drug effects* / Q000378:metabolism; D018722:Nicotinic Agonists / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D001597:Benzylidene Compounds; D007527:Isoenzymes; D018722:Nicotinic Agonists; D011725:Pyridines; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases