Authors: Yun, H.-Y.¹; Park, H.-C.¹; Kang, W.²; Kwon, K.-I.¹

Source: Journal of Clinical Pharmacy & Therapeutics, Volume 31, Number 5, October 2006 , pp. 469-476(8)

Publisher: Wiley-Blackwell

Abstract:

Summary

Glimepiride is an oral sulfonylurea antihyperglycaemic agent. We used pharmacokinetic-pharmacodynamic (PK-PD) modelling to analyse the relationship between plasma glimepiride concentration, insulin secretion and glucose lowering to determine the effects of the drug in healthy volunteers. A single 2-mg oral dose of glimepiride was administered to six healthy volunteers. The control group received a placebo. All subjects consumed 12 g of sugar immediately after drug administration in order to standardize the initial plasma glucose levels. Serial blood sampling was performed for 9 h after oral dosing. Plasma glimepiride, insulin and glucose levels were determined by validated methods (LC/MS/MS assay, hexokinase method and radioimmunoassay respectively). Time courses of plasma glimepiride concentration, insulin secretion, and glucose lowering effects were analysed by means of PK-PD modelling with the ADAPT II program. The time course of the plasma concentrations followed a two-compartmental model with a lag time. The glimepiride concentration peaked at 191·5 ng/mL at approximately 4 h after administration. The maximal increase in insulin secretion was 9·98 mIU/L and the maximal decrease in plasma glucose was 19·33 mg/dL. Both peak effects occurred at approximately 2·5 h after drug intake. The glucose disappearance model was used to analyse glimepiride's insulin secretion and glucose lowering effects. The PK-PD model described well the relationship between plasma glimepiride and its insulin secretion and hypoglycaemic effects in healthy volunteers.

Keywords: glimepiride; pharmacodynamic; pharmacokinetic; pharmacokinetic-pharmacodynamic modelling

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2710.2006.00766.x

Affiliations: 1: College of Pharmacy, Chungnam National University, Daejeon, Korea 2: Department of pharmacy, Catholic University of Daegu, Daegu, Korea

Publication date: 2006-10-01

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