Monitoring of concentrations of clobazam and norclobazam in serum and saliva of children with epilepsy

Abstract

Clobazam was added to the previous antiepileptic drug therapy of 90 children suffering from drug resistant epilepsy. Ten patients became seizure free, although four of these later developed tolerance. Thirty-three patients experienced a decrease in seizure frequency, and 24 of these, too, developed tolerance. Forty-four patients showed no change in seizure frequency, and three experienced an increase. The best results were experienced by patients with myoclonic seizures, whereas patients with complex partial seizures usually developed tolerance. The concentrations of clobazam and its active metabolite norclobazam were measured in 251 serum and 57 saliva samples. The group of seizure-free patients had the lowest clobazam and norclobazam concentrations; tolerance was associated with the highest concentrations. Beneficial side effects were associated with low, and adverse effects with high, concentrations of norclobazam. The concentrations of clobazam and norclobazam in saliva correlated with concentrations in serum. Monitoring of serum and salivary concentrations of clobazam and norclobazam is of limited value only, and no therapeutic target range can be given.