Pharmacokinetics of gliclazide in healthy and diabetic subjects.

The pharmacokinetics of total and free gliclazide, 1-(3-azabicyclo[3,3,0]oct-3-yl)-3-(p-tolylsulfonyl)urea, a potential hypoglycemic drug, was studied in healthy (n = 12) and diabetic (n = 12) subjects. The serum level of gliclazide was determined by a high-performance liquid chromatographic method (HPLC). The free fraction of gliclazide was obtained from serum by an ultrafiltration technique using a collodion membrane. The mean adsorption of gliclazide to the membrane was approximately 50% when the membrane was used more than twice. Therefore, the gliclazide level in the filtrate was corrected by doubling the apparent value. The ratio of gliclazide-protein binding remained constant at approximately 92% in serum after administration to healthy and diabetic subjects. The mean pharmacokinetic parameters of elimination rate (ke), time to reach the peak level (tmax), elimination half-life (t 1/2), and volume of distribution (Vd) were 0.07 h-1, 2.8 h, 12.3 h, and 17.4 L, respectively. The parameters did not differ significantly between healthy and diabetic subjects or between single and successive administrations; moreover, they did not differ between the free and total drug level. Although there were intersubject variations, the therapeutic effects of oral administration of gliclazide on serum glucose and insulin levels were found in four diabetic patients. The results of this study show that the pharmacokinetics of the total gliclazide level reflect those of the free gliclazide in serum.