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

$48.00 plus tax (Refund Policy)

Download / Buy Article:



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: http://dx.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: October 1, 2008

Related content



Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
Cookie Policy
ingentaconnect 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