Ethosuximide disposition kinetics in rats.
1. Single and multiple dose disposition kinetics of ethosuximide were studied in male Sprague-Dawley rats following intravenous administration. 2. 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. 3. 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. 4. 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.
Bachmann
K
K
Department of Pharmacology, College of Pharmacy, University of Toledo, Ohio 43606.
Jahn
D
D
Yang
C
C
Schwartz
J
J
D000818:Animals; D004334:Drug Administration Schedule; D005013:Ethosuximide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains
D005013:Ethosuximide