Open AccessEffect of lopinavir and efavirenz on pharmacokinetics and pharmacodynamics of glibenclamide in diabetic rats
Author(s) -
Prashanth Vennapanja,
Ajmera Ramarao
Publication year - 2017
Publication title -
pharmaceutical and biological evaluations
Language(s) - English
Resource type - Journals
ISSN - 2394-0859
DOI - 10.26510/2394-0859.pbe.2017.38
Subject(s) - glibenclamide , lopinavir , efavirenz , pharmacology , pharmacokinetics , pharmacodynamics , ritonavir , endocrinology , chemistry , medicine , cyp3a4 , diabetes mellitus , metabolism , cytochrome p450 , human immunodeficiency virus (hiv) , immunology , viral load , antiretroviral therapy , disease , covid-19 , infectious disease (medical specialty)
Objective: The aim of the study is whether the impact of Efavirenz and Lopinavir will increase the plasma level of Glibenclamide or not. Efavirenz and Lopinavir is an antiretroviral drug to treat HIV AIDS and inhibits cytochrome P450-3A4. Multiple CYP isoforms are involved in the metabolism of Glibenclamide like CYP2C8 and CYP3A4. Hence there is more possibility of Efavirenz and Lopinavir to inhibit the metabolism of Glibenclamide by inhibiting CYP 3A4.Methods: Efavirenz and Lopinavir (10 mg/kg,p.o.) alone and along with Glibenclamide (10 mg/kg, p.o.) was given to normal and diabetic rats. PK/PD parameters were studied. In the rats co-treated with Efavirenz and Lopinavir and Glibenclamide.Results: The pharmacokinetic parameters like clearance of Glibenclamide was reduced, peak plasma concentration, area under the plasma concentration time curve and elimination half-life were significantly increased when compared to pioglitazone treated rats.Conclusions: This study revealed that lopinavir and efavirenz affected the disposition of Glibenclamide in rats probably by the inhibition of CYP3A4, leading to increasing Glibenclamide concentrations that could increase the efficacy of Glibenclamide or it may causes severe hypoglycemia. Therefore, its warrants to use relatively less dose of Glibenclamide than the normal dose.