Dose linearity assessment of glimepiride (Amaryl) tablets in healthy volunteers.

Twelve healthy fasting male volunteers received glimepiride in 1, 2, 4 or 8 mg single oral doses. On the days when glimepiride was taken, the subjects were given a standardised carbohydrate diet (18 bread exchange units) and drank 125 ml of water hourly. Blood and urine samples were taken before drug administration and afterwards for up to 36 hours (blood) and 48 hours (urine) to determine serum and urinary concentrations of glimepiride and its hydroxy- and carboxy-metabolites (M1 and M2). The areas under the curve for glimepiride after oral doses of 1 to 8 mg and the urinary recovery of its metabolites M1 and M2 were dose linear. All confidence intervals were well contained within the bioequivalence range of 80-125%. There was a statistically significant difference for Cmax values of glimepiride between doses after dose normalisation. A dose-dependent increase for Cmax was nevertheless clearly observed with a correlation coefficient of r=0.90. The pharmacokinetics of glimepiride are dose linear in the dose range 1 to 8 mg, and glimepiride was safe and well tolerated in healthy volunteers.