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Pharmacokinetic and pharmacodynamic modelling of the effects of glimepiride on insulin secretion and glucose lowering in healthy humans
Author(s) -
Yun H.Y.,
Park H.C.,
Kang W.,
Kwon K.I.
Publication year - 2006
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2006.00766.x
Subject(s) - glimepiride , sulfonylurea , pharmacokinetics , pharmacodynamics , insulin , medicine , endocrinology , hypoglycemia , pharmacology , oral administration , metformin
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.