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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Dove Medical Press,
2016-09-01T00:00:00Z.
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| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_ef245e3baff44c9da0e8c9768f2374d2 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Rambiritch V |e author |
| 700 | 1 | 0 | |a Naidoo P |e author |
| 700 | 1 | 0 | |a Pillai G |e author |
| 245 | 0 | 0 | |a Glibenclamide population pharmacokinetic/pharmacodynamic modeling in South African type 2 diabetic subjects |
| 260 | |b Dove Medical Press, |c 2016-09-01T00:00:00Z. | ||
| 500 | |a 1179-1438 | ||
| 520 | |a 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 | ||
| 546 | |a EN | ||
| 690 | |a type 2 diabetes | ||
| 690 | |a glibenclamide | ||
| 690 | |a pharmacokinetic-pharmacodynamic modeling | ||
| 690 | |a dose response relationships | ||
| 690 | |a NONMEM | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Clinical Pharmacology: Advances and Applications, Vol Volume 8, Pp 141-153 (2016) | |
| 787 | 0 | |n https://www.dovepress.com/glibenclamide-population-pharmacokineticpharmacodynamic-modeling-in-so-peer-reviewed-article-CPAA | |
| 787 | 0 | |n https://doaj.org/toc/1179-1438 | |
| 856 | 4 | 1 | |u https://doaj.org/article/ef245e3baff44c9da0e8c9768f2374d2 |z Connect to this object online. |