Changes in clearance of sodium valproate with changes in dose.

Abstract

The relationship between total sodium valproate concentrations and drug clearance was studied in four patients, by the evaluation of clearance at two different doses. In each patient, the average unbound fraction for a dosing interval increased with increase in sodium valproate dose. Despite this increase in unbound fraction, there was no increase in total drug clearance, and in each patient there was a decrease in clearance of the unbound drug. These findings suggest either that the drug is restrictively cleared and there is a dose-related decline in intrinsic clearance, or, contrary to previous reports, that sodium valproate is cleared nonrestrictively.