Use of saliva for monitoring oxcarbazepine therapy in epileptic patients

Abstract

The utility of saliva sampling in monitoring oxcarbazepine therapy has been assessed in 17 epileptic outpatients treated with a mean dose 22.7 mg/kg/d for 19-411 days, i.e. at steady-state. Blood was collected before the morning dose measurement of the plasma 10-OH-carbazepine concentration and determination of the protein bound fraction. Immediately after blood sampling resting saliva and saliva produced after a masticatory stimulus were collected. Using equilibrium dialysis and an ultrafiltration technique the protein binding of 10-OH-carbazepine was found to be 40% and 45%, respectively. When the degree of protein binding was expressed as the ratio between the corresponding saliva and plasma concentrations of 10-OH-carbazepine, the concentration in resting saliva indicated that no drug was bound to plasma protein, whereas the use of stimulated saliva suggested a protein-bound fraction of 35%. The concentration in stimulated saliva reflects the free fraction of 10-OH-carbazepine, but regression analysis of paired salivary and plasma values showed that the prediction of plasma concentrations from levels in saliva is uncertain. This, together with the low degree of plasma protein binding, leads to the conclusion that it would be preferable to monitor total plasma concentrations if therapeutic drug monitoring of oxcarbazepine were to prove essential in epileptic patients.