title: Effects of cyclosporin A and itraconazole on the pharmacokinetics of atorvastatin in rats.
abstract: OBJECTIVE
  To evaluate the effects of cyclosporin A and itraconazole, which were used as inhibitors of P-glycoprotein (P-gp) and/or cytochrome P450 (CYP) 3A4 on the pharmacokinetics of atorvastatin in rats.
  
  
  METHODS
  The pharmacokinetic parameters of atorvastatin were measured after intravenous (2 mg/kg) and intragastric (10 mg/kg) administration of atorvastatin in rats, which were pretreated with cyclosporin A (5, 10, and 20 mg/kg) or itraconazole (5, 10, and 20 mg/kg).
  
  
  RESULTS
  Compared with the control rats, cyclosporin A and itraconazole altered the pharmacokinetics of atorvastatin significantly. The AUC0-t values of atorvastatin after intragastric administration, pretreated with cyclosporin A (5-20 mg/kg), increased by 32.3%, 61.8%, and 187.2%, respectively, but the CLbile values decreased (P<0.01, 5-20 mg/kg). With pretreatment of itraconazole (5-20 mg/kg), the AUC(0-t) values of atorvastatin increased by 88.2%, 102%, and 123%, respectively, but the CL(bile) values decreased (P<0.01, 5-20 mg/kg).
  
  
  CONCLUSIONS
  These data indicated that cyclosporin A could be effective in inhibiting the efflux of atorvastatin, and itraconazole could be effective in inhibiting both the metabolism and biliary excretion of atorvastatin.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Xue
authors.initials: X
authors.lastname: Yu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Ye-bin
authors.initials: YB
authors.lastname: Sun
authors.forename: Xi-jing
authors.initials: XJ
authors.lastname: Chen
authors.forename: Guang-ji
authors.initials: GJ
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001646:Bile / Q000378:metabolism; D002138:Calibration; D016572:Cyclosporine / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D017964:Itraconazole / Q000494:pharmacology*; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000935:Antifungal Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D011758:Pyrroles; D017964:Itraconazole; D016572:Cyclosporine; D000069059:Atorvastatin; D051544:Cytochrome P-450 CYP3A