Journal: Journal of Pharmacy Research

Article Id: JPRS-P'Col-00001470
Title: Effects of ritonavir on the pharmacokinetics and pharmacodynamics of pioglitazone in normal and diabetic rats
Category: Pharmacology
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    The aim of the study is whether the impact of ritonavir will increase the plasma level of pioglitazone or not. Ritonavir is an antiretroviral drug to treat HIV AIDS and inhibits cytochrome P450-3A4. Multiple CYP isoforms are involved in the metabolism of pioglitazone like CYP2C8 and CYP3A4. Hence there is more possibility of ritonavir to inhibit the metabolism of pioglitazone by inhibiting CYP 3A4. Ritonavir (10 mg/kg,p.o.)  alone and alongwith pioglitazone (10mg/kg, p.o.) was given to normal and diabetic rats. PK/PD parameters were studied. In the rats co-treated with ritonavir and pioglitazone, fasting plasma glucose concentration (58.93±3.20%) was further reduced. The pharmacokinetic parameters like clearance (12.20±0.625 l/hr) of pioglitazone was reduced, peak plasma concentration (16.78±1.08ug/ml), area under the plasma concentration time curve (163.5±14.82ug/ml/hr) and elimination half-life (6.194±0.81hr) were significantly increased when compared to pioglitazone treated rats.This study revealed that ritonavir affected the disposition of pioglitazone in rats probably by the inhibition of CYP3A4, leading to increasing pioglitazone concentrations that could increase the efficacy of pioglitazone or it may causes severe hypoglycemia. Therefore, its warrants to use relatively less dose of pioglitazone than the normal dose required for the beneficial effect on hyperlipidamia induced by ritonavir. 

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    Author(s) Name:

    Prasad Neerati*;  Keerthana Chenna.

    Affiliation(s) Name:

    DMPK & Clinical Pharmacology Division. Department of Pharmacology,
    University College of Pharmaceutical Sciences,  Kakatiya University, Warangal, AP, India.

    *Corresponding author.
    Dr .Neerati Prasad
    M.Pharm., Ph.D.
    Assistant Professor of Pharmacy
    DMPK & Clinical Pharmacology Division
    Department of Pharmacology, University College of Pharmaceutical Sciences,
    Kakatiya University,
    Warangal , AP,  India.

    Received on:10-11-2011; Revised  on: 15-12-2011; Accepted on:12-01-2012

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    Author:

    Prasad Neerati*;  Keerthana Chenna.

    Title:Effects of ritonavir on the pharmacokinetics and pharmacodynamics of pioglitazone in normal and diabetic rats
    Journal:Journal of Pharmacy Research
    Vol(issue):5 (February)
    Year:2012
    Page No: (958-962)
  • Experimental Methods Keywords

    Methodology:Cytochrome P-450 3A4, Metabolism, drug-drug interactions, Diabetes Mellitus, Pharmacokinetics & Pharmacodynamics.
    Research Materials:pioglitazone

Keywords

Cytochrome P-450 3A4 Metabolism drug-drug interactions Diabetes Mellitus Pharmacokinetics & Pharmacodynamics.

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