Ethosuximide kinetics: Possible interaction with valproic acid

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Abstract
Ethosuximide [an anticonvulsant] kinetics were determined in 6 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/h per kg (P < 0.05) and nonrenal clearance fell from 10.1 to 8.3 ml/h per 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/h per 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 7 of the 10 patients showed evidence of a nonlinear relationship when steady-state ethosuximide concentrations were plotted against dose.

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