Effects of Age and Antiepileptic Drugs on Plasma Levels and Kinetics of Clobazam and N‐Desmethylclobazam

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Abstract
The authors monitored the plasma levels of clobazam (CLO) and its principal metabolite, N‐desmethylclobazam (NCLO) during chronic treatment of more than 400 epileptic patients receiving different co‐medications, such as phenytoin (PH), carbamazepine (CBZ), sodium valproate (VPA) and phenobarbital (PB). This study investigated the influence of age and antiepileptic drugs on plasma levels of CLO and NCLO. Plasma concentrations measured 3 hr after morning administration of CLO varied from 30 to 700 ng/ml/mg/kg/d for CLO, and from 160 to 7000 ng/ml/mg/kg/d for NCLO. Plasma levels of CLO were higher in patients aged 20–30 years. NCLO concentrations increased with age up to 20 years. Coadministered antiepileptic compounds significantly decreased maximal plasma levels of CLO. Moreover, PH and CBZ a significantly increased the plasma levels of NCLO. Results on the influence of CBZ on CLO kinetics were confirmed in a group of ten patients receiving PB and VPA and later PB, VPA and CBZ as CLO associated drugs. The influence of VPA on the pharmacokinetics parameters of CLO was also evaluated in a patient in the latter group.