title: Pharmacokinetic of four probe drugs in adriamycin-induced nephropathy rat.
abstract: OBJECTIVE
  Probe drugs have been widely used to assess the activities of various CYP450 (cytochromes P450) isoenzymes in many fields of drug metabolism and pharmacogenetics. The nephrotic syndrome characterized by massive proteinuria and hypoproteinemia, whether that would influence the pharmacokinetics of probe drugs or not is still unclear. The purpose of the study was to investigate the pharmacokinetic of four probe drugs in adriamycin (ADR)-induced nephropathy rat.
  
  
  METHODS
  The rats were randomly divided into Control-group (n = 10) and ADR-group (n = 10). Nephrotic syndrome was established by weekly injections of ADR for 2 weeks. After dynamic monitoring of 24-h total urinary protein for 4 weeks, we confirmed that nephrotic syndrome had developed. The rats were administered intragastrically with phenacetin, tolbutamide, omeprazole and bupropion (15, 5, 15, and 15 mg/kg, respectively). The blood samples were determined by LC-MS (Liquid Chromatography-Mass Spectrometry) method.
  
  
  RESULTS
  The pharmacokinetics parameter of tolbutamide in ADR-group and Control-group were AUC(0-t) 15.371 ± 4.107, 6.901 ± 5.738 (mg/L*h), MRT(0-t) 8.751 ± 0.754, 6.032 ± 0.63 (h), t1/2 3.88 ± 0.423, 3.602 ± 0.693 (h), Tmax 6.2 ± 3.768, 1.95 ± 0.798 (h), CL/F 0.038 ± 0.005, 0.107 ± 0.037 (L/h/kg), V/F 0.212 ± 0.043, 0.567 ± 0.258 (L/kg), Cmax 1.853 ± 0.384, 1.422 ± 1.312 (mg/L). There was statistical difference in AUC, MRT, CL, V and Tmax of tolbutamide between two groups (p < 0.05), but no pharmacokinetics difference for phenacetin, bupropion and omeprazole.
  
  
  CONCLUSIONS
  The pharmacokinetics of tolbutamide was changed in ADR-induced nephropathy rat. It is not suitable for tolbutamide to evaluate the activity of CYP450 in nephrotic syndrome.
authors.affiliation: The Affiliated Yueqing Hospital of Wenzhou Medical University, Yuecheng Town, Yueqing City, China. hulufeng79@sina.com.
authors.forename: Z-B
authors.initials: ZB
authors.lastname: Chen
authors.forename: A Y
authors.initials: AY
authors.lastname: Zhi
authors.forename: F-Y
authors.initials: FY
authors.lastname: Lin
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: X-G
authors.initials: XG
authors.lastname: Yu
authors.forename: W-H
authors.initials: WH
authors.lastname: Chen
authors.forename: L-F
authors.initials: LF
authors.lastname: Hu
mesh_terms: D000818:Animals; D016642:Bupropion / Q000097:blood / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004317:Doxorubicin; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D009853:Omeprazole / Q000097:blood / Q000493:pharmacokinetics*; D010615:Phenacetin / Q000097:blood / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D016642:Bupropion; D004317:Doxorubicin; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D010615:Phenacetin; D009853:Omeprazole