Influence of Efavirenz and Nevirapine on the Pharmacodynamics and Pharmacokinetics of Gliclazide in Rabbits

Kilari Eswar Kumar, Shaik Mastan

Abstract


Background: Since polypharmacy is very common practice in diabetic patients, the study of drug-drug interactions is an imperative rational approach with respect to safety and efficacy determination. Gliclazide is a widely used drug for the treatment of type 2 diabetes. Efavirenz and nevirapine are widely used non-nucleoside reverse transcriptase inhibitors (NNRTIs) with fewer side effects concerning diabetic complications.The objective of the study is to investigate the effect of selected NNRTIs on the pharmacodynamics and pharmacokinetics of gliclazide in rabbits with respect to safety and efficacy of the combination.

Methods: Influence of selected NNRTIs on the activity of gliclazide was determined by conducting a single dose interaction followed by multiple dose interaction study with two groups consisting of 6 normal rabbits each. Each group was treated with an oral dose of 5.6 mg/1.5 kg bd. wt. of gliclazide, interacting drug treatment (42 mg/1.5 kg bd. wt. of efavirenz or 14 mg/1.5 kg bd. wt. of nevirapine) and their combination with a one week washout period between each treatment. One week washout after this single dose interaction study, each group was continued with the daily treatment of interacting drug for the next eight days and then the combined treatment on the ninth day. Blood samples were collected at regular intervals by marginal ear vein puncture in rabbits and were analyzed for blood glucose by GOD/POD method and insulin by radioimmunoassay method. The serum gliclazide levels were estimated by HPLC method and pharmacokinetic analysis was conducted by noncompartmental analysis using WinNonlin software.

Results: In combination, efavirenz significantly (P less than 0.05) reduced the pharmacodynamic activity and serum levels of gliclazide. The pharmacokinetic parameters of gliclazide were significantly (P less than 0.05) altered. The percent decrease of serum gliclazide concentration level is 24.23% and 15.20% following single dose and multiple dose administration of efavirenz, respectively. In combination, nevirapine has no significant effect on the pharmacodynamics and pharmacokinetics of gliclazide in rabbits.

Conclusions: The significant pharmacokinetic interaction of efavirenz at metabolic level by CYP3A4 induction results in decreased serum gliclazide levels and pharmacodynamic activity of gliclazide. The combination of nevirapine and gliclazide was proved to be safe.



doi:10.4021/jem34w


Keywords


Gliclazide; Efavirenz; Nevirapine; Diabetes; HIV infection; Pharmacokinetics

Full Text: HTML PDF
 
Home     |     Log In     |      About     |      Search     |      Current     |      Archives     |      Submit      |     Subscribe


 

     

Aims and Scope

Current Issues

Conflict of Interest

About Publisher

Editorial Board

Archives

Copyright

Company Profile

Editorial Office

Misconduct and Retraction

Permissions

Company Registration

Contact Us

Abstracting and Indexing

ICMJE

Ownership

Instructions to Authors

Access

Declaration of Helsinki

Contact Publisher

Submission Checklist

Reprints

Terms of Use

Company Address

Submit a Manuscript

Open Access Policy

Privacy Policy

Browse Journals

Publishing Fee

Publishing Policy

Disclaimer

Recent Highlights

Peer-Review Process

Publishing Quality

Code of Ethics

Advertising Policy

Manuscript Tracking

Advanced Search

For Librarians

Careers

Publishing Process

Publication Frequency

For Reviewers

Propose a New Journal

       
       

Journal of Endocrinology and Metabolism, bimonthly, ISSN 1923-2861 (print), 1923-287X (online), published by Elmer Press Inc.        
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.jofem.org   editorial contact: editor@jofem.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.

DECLARATION: THIS JOURNAL SITE OUTLOOK IS DESIGNED BY THE PUBLISHER AND COPYRIGHT PROTECTED. DO NOT COPY!