Pharmacokinetic changes of ipriflavone in rats with acute renal failure induced by uranyl nitrate.
Pharmacokinetic parameters of ipriflavone were compared after intravenous (20 mg/kg) and oral (200 mg/kg) administration in control rats and in rats with acute renal failure induced by uranyl nitrate (U-ARF rats). It was expected that the time-averaged nonrenal clearance (Cl(nr)) of ipriflavone in U-ARF rats could be significantly slower than in the control rats, since it was reported that ipriflavone was metabolized via the hepatic microsomal cytochrome P450 (CYP) 1A1/2 and 2C11 and the expression and mRNA level of CYP1A2 were not changed, but those of CYP2C11 were decreased in U-ARF rats compared with control rats. Unexpectedly, after intravenous administration in U-ARF rats, the Cl(nr) of ipriflavone was significantly faster than in the controls (40.8 compared with 29.0 ml/min/kg). This may be due to an increase in the glucuronide conjugate formation of ipriflavone metabolites in U-ARF rats. After oral administration of ipriflavone in U-ARF rats, the AUC(0-24 h) was significantly smaller (194 compared with 295 microg min/ml) than in the controls.
Chung
Hye J
HJ
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D007275:Injections, Intravenous; D007529:Isoflavones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000097:blood / Q000139:chemically induced*; D014502:Uranyl Nitrate / Q000633:toxicity*
D007529:Isoflavones; D014502:Uranyl Nitrate; C018986:ipriflavone