INFLUENCE OF FOOD-INTAKE ON THE PHARMACOKINETICS OF A SUSTAINED-RELEASE FORMULATION OF SODIUM VALPROATE

The effect of food intake on the pharmacokinetics of DEPAKINE(R) CHRON O 500 mg (Sanofi, France), a sustained release formulation containing 333 mg sodium valproate and 145 mg valproic acid, was studied in 12 yo ung healthy female volunteers. Relative to fasting conditions (F), whe n the tablet was given at the midpoint of the breakfast (NF), the maxi mum concentration (F: 34.6+/-8.9 mug ml-1 and NF: 40.9+/-7.3 mug ml-1; p = 0.014) and the mean cumulative amount absorbed up to time 6 h (F: 76-3+/-11.8% and NF: 90+/-10.4%; p = 0.0099) were significantly incre ased. Nevertheless, the extent of absorption(F: 46.7+/-9.9 mg l-1; NF: 48.7+/-7 mg l-1) was not significantly affected. There was no change in the area under the curve (1129 mug.h ml-1), in the mean residence t ime (28 h), or in the elimination half-life (16 h). On the basis of th is study, the question as to whether DEPAKINE(R) CHRONO should be admi nistered to subjects in the fasting or non-fasting state would not app ear to be a major consideration when deciding on the regimen.