Ethosuximide disposition kinetics in rats

Abstract

Single and multiple dose disposition kinetics of ethosuximide were studied in male Sprague-Dawley rats following intravenous administration. The plasma disappearance of a single 35 mg/kg dose followed for 75 h was not linear. A dose-ranging study suggested that the apparent non-linearity of ethosuximide''s plasma disappearance might be due to enzyme induction over time with the drug exhibiting a faster elimination from 24 h onward. Ethosuximide, after only two daily doses of 35 mg/kg/day, shortened pentobarbital-induced sleep in rats. The clearance of ethosuximide was also significantly faster after four daily 35 mg/kg doses than after a single 35 mg/kg dose. Single sample clearance estimates calculated from ethosuximide concentrations prior to enzyme induction, viz. up to 24 h post-dose, were practically identical to multiple sample clearance values. Both single and multiple sample clearances were calculated assuming linear rather than non-linear elimination.