Evaluation of Clonazepam Pharmacokinetics in Epileptic Children Receiving Monotherapy or Polytherapy, and the Influences of Concomitant Antiepileptic Drugs on the Serum Concentration of Clonazepam

Abstract

We investigated the relationship between the steady-state serum concentration of clonazepam and the daily dose per weight in epileptic children under 12 years of age who were receiving chronic monotherapy or polytherapy. We also examined the effects of the concurrent administration of other antiepileptic drugs, including phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), zonisamide (ZNS), and valproic acid (VPA), on the serum concentration of clonazepam by multiple linear regression analysis. The clonazepam concentration in the same daily dose and the concentration/dose ratio were lower in the polytherapy group than in the monotherapy group. The clonazepam concentration was noted to be positively proportional to the dose of clonazepam and was negatively affected by the addition of PB, PHT, and CBZ, but not of ZNS or VPA. The present results suggest that the differences of clonazepam pharmacokinetics in the monotherapy and polytherapy are associated with the effects of PB, PHT, and CBZ on the serum concentration of clonazepam.