4'-hydroxylation of flurbiprofen by rat liver microsomes in fasting and feeding conditions.
We examined the 4'-hydroxylation of flurbiprofen in rat hepatocytes and liver microsomes in order to know whether the metabolism of flurbiprofen is changed on its administration to experimental animals after overnight fasting, because starvation and fasting change both the composition of cytochrome P450s (CYPs) and metabolic activity. CYPs involved in the hydroxylation were determined by various CYP inhibitors and inhibitory antibodies against rat CYP2C11 and CYP2E1 using the microsomes in fasting and feeding. The results provided a possibiliy that the 4'-hydroxylation might be regulated by CYP2C11, but not by CYP2E1, at fasting rather than feeding.
Shimizu
Makiko
M
Department of Clinical Pharmacology and Toxicology, Showa Pharmaceutical University, Japan. shimizu@ac.shoyaku.ac.jp
Matsushita
Reiko
R
Matsumoto
Yoshiaki
Y
Fukuoka
Masamichi
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005480:Flurbiprofen / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D005480:Flurbiprofen