title: Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of liquiritigenin and its two glucuronides, M1 and M2, in rats.
abstract: OBJECTIVE
  Liver disease and acute renal failure (ARF) are closely associated. The pharmacokinetics of liquiritigenin (LQ), a candidate therapy for inflammatory liver disease, and its metabolites M1 and M2 were evaluated in rats with ARF induced by uranyl nitrate (U-ARF rats).
  
  
  METHODS
  LQ was administered intravenously (20 mg/kg) or orally (50 mg/kg) in U-ARF and control rats, and uridine diphosphate-glucuronosyltransferases (UGT) activity and uridine 5'-diphosphoglucuronic acid (UDPGA) concentrations were determined in the liver and intestine.
  
  
  RESULTS
  After intravenous LQ administration, U-ARF rats displayed significantly slower LQ renal clearance but no significant changes in the LQ area under the plasma concentration-time curve (AUC) compared with controls. This was because of similar hepatic UGT activity and UDPGA levels between two groups, which resulted in comparable non-renal clearance, as well as the limited contribution of LQ renal clearance to total LQ clearance. However, the AUC and AUC(M) /AUC(LQ) ratios of M1 and M2 were significantly increased in U-ARF rats because of decreased urinary excretion of M1 and M2. Similar results were observed following oral administration because of the comparable LQ intestinal metabolism in both groups and decreased urinary excretion of M1 and M2 in U-ARF rats.
  
  
  CONCLUSIONS
  U-ARF rats displayed decreased urinary excretion of LQ glucuronides, resulting in significantly greater AUC and metabolite ratios of M1 and M2 following LQ administration.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Hee E
authors.initials: HE
authors.lastname: Kang
authors.forename: Se I
authors.initials: SI
authors.lastname: Sohn
authors.forename: Seung R
authors.initials: SR
authors.lastname: Baek
authors.forename: Jee W
authors.initials: JW
authors.lastname: Lee
authors.forename: Myung G
authors.initials: MG
authors.lastname: Lee
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications*; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D044950:Flavanones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014502:Uranyl Nitrate / Q000633:toxicity; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism
chemical_list: D044950:Flavanones; D020719:Glucuronides; D014502:Uranyl Nitrate; D014535:Uridine Diphosphate Glucuronic Acid; D014453:Glucuronosyltransferase; C083152:liquiritigenin