Skip to main content

Effects of cyclosporin A and itraconazole on the pharmacokinetics of atorvastatin in rats

Buy Article:

$51.00 plus tax (Refund Policy)

Abstract:

Abstract

Aim: 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 intra-gastric (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 AUC0-t values of atorvastatin increased by 88.2%, 102%, and 123%, respectively, but the CLbile values decreased (P<0.01, 5–20 mg/kg). Conclusion: 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.

Keywords: P-glycoprotein; atorvastatin; cyclosporin A; cytochrome P450 (CYP) 3A4; itraconazole; pharamcokinetics

Document Type: Research Article

DOI: https://doi.org/10.1111/j.1745-7254.2008.00858.x

Affiliations: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

Publication date: 2008-10-01

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more