Dose Linearity of Glimepiride in Healthy Human Egyptian Volunteers.

The present study was adopted to evaluate the pharmacokinetics and dose linearity of glimepiride after administration of single oral doses of 1-6 mg glimepiride in an open-label, five-way crossover study. Twenty-four healthy male Egyptian volunteers were given 1, 2, 3, 4, and 6 mg of glimepiride on five occasions, and blood samples were collected over 24 hours. Plasma glimepiride concentrations were assayed by a validated reversed-phase high-performance liquid chromatography method with UV detection and the data were evaluated by non-compartmental methods to determine pharmacokinetic parameters. The mean elimination half-lives (t1/2 ) did not vary with the dose. The peak plasma levels (Cmax ) and area under the plasma level versus time curve (AUC) data showed dose-proportional response. The time to peak plasma concentration (tmax ), mean residence time, oral clearance (Cl/F) and apparent volume of distribution (Vd /F) were all similar regardless of the administered dose (P > .05). The 90% confidence intervals of the ratios of dose-adjusted log transformed values of Cmax , AUC0-t , AUC0-∞ , t1/2 , and tmax fell within the range of 80-125%. These findings suggest that glimepiride disposition is linear over the dose range studied healthy human Egyptian volunteers.