IPSIndian Journal of Pharmacology
Home  IPS  Feedback Subscribe Top cited articles Login 
Users Online : 9003 
Small font sizeDefault font sizeIncrease font size
Navigate Here
 »   Next article
 »   Previous article
 »   Table of Contents

Resource Links
 »   Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »   Citation Manager
 »   Access Statistics
 »   Reader Comments
 »   Email Alert *
 »   Add to My List *
 * Requires registration (Free)

 Article Access Statistics
    PDF Downloaded146    
    Comments [Add]    
    Cited by others 6    

Recommend this journal


Year : 2012  |  Volume : 44  |  Issue : 5  |  Page : 624-628

Effects of pravastatin on the pharmacokinetic parameters of nimodipine after oral and intravenous administration in rats: Possible role of CYP3A4 inhibition by pravastatin

1 Department of Medical Management, Chodang University, Mooan, Korea
2 Department of Pharmaceutics, College of Pharmacy, Gwangju, Korea
3 Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea

Correspondence Address:
Dong-Hyun Choi
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0253-7613.100395

Rights and Permissions

Objective: The aim of this study was to investigate the effects of pravastatin on the pharmacokinetics of nimodipine in rats. Materials and Methods: The effect of pravastatin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Nimodipine was administered to rats intravenously (3 mg/kg) and orally (12 mg/kg) with pravastatin (0.3 and 1 mg/kg). Results: Pravastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC 50 ) of 14 ΅M. Compared with the oral control group, the area under the plasma concentration-time curve (AUC 0-∞ ) of nimodipine was increased significantly. Consequently, the absolute bioavailability (AB) of nimodipine with pravastatin (1 mg/kg) was 31.1%, which was significantly enhanced compared with the oral control group. Moreover, the relative bioavailability (RB) of nimodipine was 1.12- to 1.31-fold greater than that of the control group. Conclusions: The enhanced oral bioavailability of nimodipine might be mainly due to inhibition of the CYP3A-mediated metabolism of nimodipine in the small intestine and/or in the liver and due to reduction of the total body clearance rather than both to inhibition of the P-gp efflux transporter in the small intestine and reduction of renal elimination of nimodipine by pravastatin. The increase in the oral bioavailability of nimodipine with pravastatin should be taken into consideration of potential drug interactions between nimodipine and pravastatin.


Print this article     Email this article

Site Map | Home | Contact Us | Feedback | Copyright and Disclaimer | Privacy Notice
Online since 20th July '04
Published by Wolters Kluwer - Medknow