Sodium valproate: dose-plasma level relationships and interdose fluctuations

Abstract

Individual dose-plasma level relationships were studied in 14 chronically treated epileptics, 10 of whom were concomitantly receiving other anticonvulsants besides valproate. Linear regression analysis showed each individual relationship to be linear with correlation co-efficients ranging from 0.9137 to 0.9997. A considerable inter-individual variation was found to exist in the slopes of the regression lines (range: 0.86 to 5.72). This may be the consequence of differences in absorption characteristics and metabolic handling of the drug. The results indicate that a proportional rise in plasma sodium valproate levels can be expected following dosage increments in an individual patient. Hourly plasma sodium valproate measurements for 6 hours between 2 successive doses, in the same group of patients, showed that the mean percentage change in post-dose peak plasma levels was 44.5%, and range from 20.7 to 153.5%. Plasma levels returned to values close to pre-dose starting levels 6 hours after the administration of a dose. The large degree of inter-dose fluctuation between doses indicates that it is preferable to use pre-dose plasma sodium valproate levels to guide the clinical management of epileptic patients.