The relationship between the pharmacokinetics of gliclazide and its antidiabetic efficacy were evaluated on the basis of experimental determination of changes with time in the plasma levels of this antidiabetic agent and those of glucose. The experiment included rats with both initial normal glycaemia and alloxan-induced hyperglycaemia (glycaemia increased by a minimum of 30%). Pharmacokinetic and pharmacodynamic parameters were examined in the interval of 30 to 180 min after p.o. administration of a single dose of 25 mg/kg of gliclazide. The drug was administered on day 4, following a single i.v. dose of either 50 mg/kg of alloxan (hyperglycaemic group) or the injection vehicle (control group). Even though the biological availability of gliclazide was similar in both normoglycaemic and hyperglycaemic animals, the gliclazide-induced hypoglycaemizing response was not uniform: until 60 min, the decrease of glycaemia was smaller in animals with alloxan hyperglycaemia (23% decrease at 60 min) in contrast to the normoglycaemic animals (36% decrease at 60 min), at later times, the intensity of this hypoglycaemizing effect of gliclazide persisted in the hyperglycaemic animals, while in the normoglycaemic ones, a reversal of the hypoglycaemizing effect occurred. Copyright (c) 2007 John Wiley & Sons, Ltd.

Institute of Experimental Biopharmaceutics Joint Research Centre of the Czech Academy of Sciences and PRO MED CS Praha a s Hradec Kralove Czech Republic