A dose proportionality study of eprosartan in healthy male volunteers

The present study investigated the proportionality of exposure after single oral doses of 100, 200, 400, and 800 mg of eprosartan, a nonpeptide, nonbiphenyl angiotensin II receptor antagonist, in 23 healthy young men. Eprosartan was safe and well tolerated. Exposure to eprosartan increased with dose but in a less than proportional manner. For each two-fold dose increase, area under the concentration-time curve (AUC) increased an average of 1.6 to 1.8 times and maximum plasma drug concentration (C-max) increased an average of 1.5 to 1.8 times. For both parameters, the greatest difference from the dose multiple rt as observed between the 400- and 800-mg doses. Dose proportionality of eprosartan, as assessed by an equivalence-type approach using the 100-mg dose as the reference and a 30% acceptance region (0.70, 1.43), was achieved for the 200- and 400-mg doses for AUC and the 200-mg dose for C-max. The observed changes in the pharmacokinetics of eprosartan suggest slight saturation of absorption of eprosartan over the 100- to 800-mg dose range, most likely due to the physicochemical properties of the drug (pH-dependent aqueous solubility and lipophilicity).