Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal models

S K Mastan1, K Eswar Kumar21Research and Development Cell, Jawaharlal Nehru Technological University, Hyderabad, Andhra Pradesh, India; 2Pharmacology Division, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, IndiaAbstract: The objective of this s...

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Main Authors: S K Mastan, K Eswar Kumar
Format: Article
Language:English
Published: Dove Medical Press 2009-12-01
Series:Journal of Experimental Pharmacology
Online Access:http://www.dovepress.com/effect-of-antiretroviral-drugs-on-the-pharmacodynamics-of-gliclazide-w-a3853
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spelling doaj-54c0aab7f5514e3484dc0fd9142f29ab2021-09-02T19:49:37ZengDove Medical PressJournal of Experimental Pharmacology1179-14542009-12-012010default111Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal modelsS K MastanK Eswar KumarS K Mastan1, K Eswar Kumar21Research and Development Cell, Jawaharlal Nehru Technological University, Hyderabad, Andhra Pradesh, India; 2Pharmacology Division, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, IndiaAbstract: The objective of this study was to investigate the effect of oral administration of antiretroviral drugs (indinavir, ritonavir, atazanavir, efavirenz and nevirapine) on the pharmacodynamics of gliclazide in rats (normal and diabetic) and rabbits with respect to glucose–insulin homeostasis to evaluate the safety and effectiveness of the combinations. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analyzed for blood glucose by glucose oxidase–peroxidase method and insulin by a radio immuno assay method. The insulin resistance index and β-cell function were determined by a homeostasis model assessment. Indinavir and ritonavir alone had significant impact on glucose–insulin homeostasis in animal models among the antiretroviral drugs used in our study. In combination, indinavir and efavirenz significantly reduced the activity of gliclazide, while ritonavir and atazanavir significantly increased the activity of gliclazide. However, nevirapine had no significant effect on the activity of gliclazide. From this study we conclude that glucose–insulin homeostasis disorders associated with antiretroviral drugs are not class-specific, but are drug-specific. So care should be taken when indinavir, ritonavir, atazanavir and efavirenz are prescribed for diabetic patients.Keywords: protease inhibitors, efavirenz, nevirapine, gliclazide, homeostasis model assessment, diabetes http://www.dovepress.com/effect-of-antiretroviral-drugs-on-the-pharmacodynamics-of-gliclazide-w-a3853
collection DOAJ
language English
format Article
sources DOAJ
author S K Mastan
K Eswar Kumar
spellingShingle S K Mastan
K Eswar Kumar
Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal models
Journal of Experimental Pharmacology
author_facet S K Mastan
K Eswar Kumar
author_sort S K Mastan
title Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal models
title_short Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal models
title_full Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal models
title_fullStr Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal models
title_full_unstemmed Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal models
title_sort effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose–insulin homeostasis in animal models
publisher Dove Medical Press
series Journal of Experimental Pharmacology
issn 1179-1454
publishDate 2009-12-01
description S K Mastan1, K Eswar Kumar21Research and Development Cell, Jawaharlal Nehru Technological University, Hyderabad, Andhra Pradesh, India; 2Pharmacology Division, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, IndiaAbstract: The objective of this study was to investigate the effect of oral administration of antiretroviral drugs (indinavir, ritonavir, atazanavir, efavirenz and nevirapine) on the pharmacodynamics of gliclazide in rats (normal and diabetic) and rabbits with respect to glucose–insulin homeostasis to evaluate the safety and effectiveness of the combinations. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analyzed for blood glucose by glucose oxidase–peroxidase method and insulin by a radio immuno assay method. The insulin resistance index and β-cell function were determined by a homeostasis model assessment. Indinavir and ritonavir alone had significant impact on glucose–insulin homeostasis in animal models among the antiretroviral drugs used in our study. In combination, indinavir and efavirenz significantly reduced the activity of gliclazide, while ritonavir and atazanavir significantly increased the activity of gliclazide. However, nevirapine had no significant effect on the activity of gliclazide. From this study we conclude that glucose–insulin homeostasis disorders associated with antiretroviral drugs are not class-specific, but are drug-specific. So care should be taken when indinavir, ritonavir, atazanavir and efavirenz are prescribed for diabetic patients.Keywords: protease inhibitors, efavirenz, nevirapine, gliclazide, homeostasis model assessment, diabetes
url http://www.dovepress.com/effect-of-antiretroviral-drugs-on-the-pharmacodynamics-of-gliclazide-w-a3853
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