Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects

Virendra Rambiritch,1 Poobalan Naidoo,2 Goonaseelan Pillai3 1Pharmacology Department, University of KwaZulu-Natal, Durban, 2Department of Internal Medicine, RK Khan Regional Hospital, Chatsworth, South Africa; 3Scientific Capability Development, Novartis Pharma AG, Basel, Switzerland Aim: To determi...

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Autores principales:	Rambiritch V, Naidoo P, Pillai G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	type 2 diabetes glibenclamide pharmacokinetic-pharmacodynamic modeling dose response relationships NONMEM Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ef245e3baff44c9da0e8c9768f2374d2
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spelling	oai:doaj.org-article:ef245e3baff44c9da0e8c9768f2374d22021-12-02T05:56:45ZGlibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects1179-1438https://doaj.org/article/ef245e3baff44c9da0e8c9768f2374d22016-09-01T00:00:00Zhttps://www.dovepress.com/glibenclamide-population-pharmacokineticpharmacodynamic-modeling-in-so-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Virendra Rambiritch,1 Poobalan Naidoo,2 Goonaseelan Pillai3 1Pharmacology Department, University of KwaZulu-Natal, Durban, 2Department of Internal Medicine, RK Khan Regional Hospital, Chatsworth, South Africa; 3Scientific Capability Development, Novartis Pharma AG, Basel, Switzerland Aim: To determine the effective dose of glibenclamide by quantifying the dose–response relationship in South African type 2 diabetic patients.Patients and methods: A total of 24 type 2 diabetic patients participated in a glibenclamide dose-escalation study during which glibenclamide, glucose, and insulin concentrations were quantified, while the dose of glibenclamide was progressively increased. All except four subjects contributed data on all dose-escalation steps; however, data from all 24 patients were included in the model-based analysis. Pharmacokinetic/pharmacodynamic (PKPD) relationships were modeled using the software Nonmem®. Six models were utilized to explore the effect of alternative glibenclamide dose and plasma concentration inputs on various metrics of glucose response.Results: Six models adequately described the experimental data. The effective dose for a glucose-lowering effect suggested by PKPD modeling is less than 5 mg/day. Doses beyond 5 mg/day do not meaningfully add to glibenclamide effects on blood-glucose response.Conclusion: The effective dose of glibenclamide, suggested by PKPD modeling, is less than 5 mg/day. Higher doses of glibenclamide, eg, 15 mg/day as originally recommended by the manufacturer, do not produce further decrease in the blood glucose level but may predispose the patients to adverse effects. Keywords: type 2 diabetes, glibenclamide, pharmacokinetic/pharmacodynamic modeling, dose–response relationships, NonmemRambiritch VNaidoo PPillai GDove Medical Pressarticletype 2 diabetesglibenclamidepharmacokinetic-pharmacodynamic modelingdose response relationshipsNONMEMTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 8, Pp 141-153 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	type 2 diabetes glibenclamide pharmacokinetic-pharmacodynamic modeling dose response relationships NONMEM Therapeutics. Pharmacology RM1-950
spellingShingle	type 2 diabetes glibenclamide pharmacokinetic-pharmacodynamic modeling dose response relationships NONMEM Therapeutics. Pharmacology RM1-950 Rambiritch V Naidoo P Pillai G Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects
description	Virendra Rambiritch,1 Poobalan Naidoo,2 Goonaseelan Pillai3 1Pharmacology Department, University of KwaZulu-Natal, Durban, 2Department of Internal Medicine, RK Khan Regional Hospital, Chatsworth, South Africa; 3Scientific Capability Development, Novartis Pharma AG, Basel, Switzerland Aim: To determine the effective dose of glibenclamide by quantifying the dose–response relationship in South African type 2 diabetic patients.Patients and methods: A total of 24 type 2 diabetic patients participated in a glibenclamide dose-escalation study during which glibenclamide, glucose, and insulin concentrations were quantified, while the dose of glibenclamide was progressively increased. All except four subjects contributed data on all dose-escalation steps; however, data from all 24 patients were included in the model-based analysis. Pharmacokinetic/pharmacodynamic (PKPD) relationships were modeled using the software Nonmem®. Six models were utilized to explore the effect of alternative glibenclamide dose and plasma concentration inputs on various metrics of glucose response.Results: Six models adequately described the experimental data. The effective dose for a glucose-lowering effect suggested by PKPD modeling is less than 5 mg/day. Doses beyond 5 mg/day do not meaningfully add to glibenclamide effects on blood-glucose response.Conclusion: The effective dose of glibenclamide, suggested by PKPD modeling, is less than 5 mg/day. Higher doses of glibenclamide, eg, 15 mg/day as originally recommended by the manufacturer, do not produce further decrease in the blood glucose level but may predispose the patients to adverse effects. Keywords: type 2 diabetes, glibenclamide, pharmacokinetic/pharmacodynamic modeling, dose–response relationships, Nonmem
format	article
author	Rambiritch V Naidoo P Pillai G
author_facet	Rambiritch V Naidoo P Pillai G
author_sort	Rambiritch V
title	Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects
title_short	Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects
title_full	Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects
title_fullStr	Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects
title_full_unstemmed	Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects
title_sort	glibenclamide population pharmacokinetic/pharmacodynamic modeling in south african type 2 diabetic subjects
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/ef245e3baff44c9da0e8c9768f2374d2
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_version_	1718400145870028800

Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects

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