Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes

Objective: We analysed the kinetics and effects of glibenclamide (Gb) on gl ucose, insulin and proinsulin secretion in two ethnic groups (10 in each) o f type-2 diabetic patients, one of Caucasian, the other of Chinese origin. Background: Diabetes mellitus type 2 is a global disease affecting all ethn ic groups. There are ethnic differences in both the prevalence and metaboli c characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. Material and methods: The patients were studied on two occasions when eithe r no Gb (control) or 1.25 mg Gb was administered i.v., immediately before t he administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net a reas under the curves, with basal values set as zero. A P value less than 0 .05 was considered significant. Results: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l x min vs 2.6 mmol /l x min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l x min vs 54 pmol/l x min) and 30 min (2286 pmol/l x min vs 1198 pmol/l x min). When Gb was administered, the plasma glucose in creases were reduced, and the increases of serum insulin and proinsulin lev els were greater in both ethnic groups. Compared with the basal values (-1 min), proinsulin/ insulin ratios (RPI) were lowest at 10-30 min, followed b y an increase. Chinese patients had higher increases of serum insulin level s at 10 min (1109 pmol/l x min vs 550 pmol/l x min) and a lower RPI at 30 m in (6.0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Seru m Gb data were best fitted to a biexponential i.v. model. There were no int erethnic differences in any of the pharmacokinetic parameters. Conclusion: In summary, following oral glucose administration without Gb, C hinese type-2 diabetic patients had higher plasma insulin levels but also h igher plasma glucose levels during the first 10 min, which might reflect re duced insulin sensitivity or more rapid glucose absorption. Gb augmented gl ucose-induced release of both insulin and proinsulin in both ethnic groups the effect on insulin secretion was more pronounced. In conclusion, minor p harmacodynamic but no pharmacokinetic differences were found between the tw o groups. It seems appropriate to employ the same dosage principles when us ing Gb in Caucasians and Chinese.