Valproic acid-ethosuximide interaction: a pharmacokinetic study.


The present pharmacokinetic study was designed to investigate the possible interaction between valproic acid (VPA) and ethosuximide (ESM) in humans. Six drug-free healthy volunteers, four men and two women, 18-42 years of age, received a single oral dose of 500 mg ESM before and during a treatment with VPA at 800- to 1,600-mg daily doses. The second ESM dose was given 9 days after VPA administration was started. In this latter condition, a significant (p less than 0.05) increase in ESM serum half-life, from 44 to 54 h on average, and a significant (p less than 0.05) decrease in total body clearance, from 11.2 to 9.5 ml/min on average, were observed. Other pharmacokinetic parameters were unchanged and showed values similar to those reported in the literature. Serum VPA levels ranged between 66.8 and 95 micrograms/ml. Two subjects showed no evidence of interaction. Although a great interindividual variability in the occurrence of VPA-ESM interaction can be observed, the present study indicates that VPA is able to inhibit the metabolism of ESM. Possible factors affecting this interaction are hypothesized and discussed.

Cite this paper

@article{Pisani1984ValproicAI, title={Valproic acid-ethosuximide interaction: a pharmacokinetic study.}, author={Francesco Pisani and Mc Narbone and C. Trunfio and Adrienne Fazio and Greg La Rosa and Giancarla Oteri and Raoul Di Perri}, journal={Epilepsia}, year={1984}, volume={25 2}, pages={229-33} }