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.

Intra-daily oscillations in dipropylacetic acid plasma levels with two or three daily doses of dipropylacetamide in epileptic patients.

The diurnal fluctuations in dipropylacetic acid (DPA) plasma levels were examined in ten epileptic patients following a chronic treatment with 3 or 2 daily doses of dipropylacetamide (DPM). The highest/lowest DPA levels ratios observed throughout 24 hrs were 1.18 and 1.36, respectively, but the difference in the data was not statistically significant (p greater than 0.05). The present results indicate that a reduction of the frequency of the daily administrations of the drug can be made with consequent possible improvement in the patient's compliance. The clinical value of the oscillations in DPA serum levels is also revised in the light of the data reported in the literature.