Premium
Ethosuximide kinetics: Possible interaction with valproic acid
Author(s) -
Bauer Larry A,
Harris Connie,
Wilensky Alan J,
Raisys Vidmantas A,
Levy Rene H
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.104
Subject(s) - ethosuximide , valproic acid , pharmacokinetics , kinetics , chemistry , steady state (chemistry) , pharmacology , anticonvulsant , medicine , epilepsy , physics , quantum mechanics , psychiatry
Ethosuximide kinetics were determined in six normal healthy adults after a single dose (phase 1) and at steady‐state (phase 2). After the completion of phase 2, valproic acid was added to the ethosuximide regimen (phase 3) to assess the possibility of drug interaction. Between phases 1 and 2 total clearance fell from 13.1 to 11.1 ml/hr/kg (P < 0.05) and nonrenal clearance fell from 10.1 to 8.3 ml/hr/kg (P < 0.05). When valproic acid was added (phase 3) there was no further change in total or nonrenal clearance (11.2 and 8.3 ml/hr/kg). To assess the possibility of nonlinear ethosuximide kinetics a review was conducted of patients who received ethosuximide as sole therapy for absence seizures. Of 106 patients, 10 met the required criterion that defined steady state. Data from seven of the 10 patients showed evidence of a nonlinear relationship when steady‐state ethosuximide concentrations were plotted against dose. Clinical Pharmacology and Therapeutics (1982) 31 , 741–745; doi: 10.1038/clpt.1982.104