Effects of E. Coli lipopolysaccharide on the pharmacokinetics of ipriflavone and its metabolites, M1 and M5, after intravenous and oral administration of ipriflavone to rats: decreased metabolism of ipriflavone due to decreased expression of hepatic CYP1A2 and 2C11.
It was reported that ipriflavone was primarily metabolized via hepatic CYP1A1/2 and 2C11 in rats. In the present study, the expression of CYP1A2 and 2C11 decreased in the liver, but increased in the intestine in rats pretreated with E. coli lipopolysaccharide (ECLPS; an animal model of inflammation). Thus, pharmacokinetic parameters of ipriflavone and its metabolites, M1 and M5, were evaluated in ECLPS rats. After intravenous administration (20 mg/kg) to ECLPS rats, the AUC of ipriflavone was significantly greater (26.7% increase) and CL(NR) of ipriflavone was significantly slower (19.9% decrease) than in the controls. This could have been due to decreased expression of hepatic CYP1A2 and 2C11 compared to the controls. After oral administration (200 mg/kg) to ECLPS rats, the AUC of ipriflavone was also significantly greater (130% increase) than in the controls. Although the expression of intestinal CYP1A2 and 2C11 increased in ECLPS rats, contribution of this increase to the significantly greater AUC of ipriflavone after oral administration of ipriflavone to ECLPS rats was not considerable. This could have also been due to a significantly decreased expression of hepatic CYP1A2 and 2C11 in ECLPS rats. The formation of M1 and M5 could be mediated via CYP1A2 and/or 2C11 in rats.
Chung
Hye J
HJ
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Kang
Hee E
HE
Bae
Eun J
EJ
Lee
Inchul
I
Kim
Sang G
SG
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D004926:Escherichia coli / Q000737:chemistry*; D007262:Infusions, Intravenous; D007529:Isoflavones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D039181:Steroid 16-alpha-Hydroxylase / Q000378:metabolism*
D007529:Isoflavones; D008070:Lipopolysaccharides; C018986:ipriflavone; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D019388:Cytochrome P-450 CYP1A2; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase