标题：Influence of Coadministered Antiepileptic Drugs on Serum Zonisamide Concentrations in Epileptic Patients: Quantitative Analysis Based on Suitable Transforming Factor
摘要：We conducted a study to clarify the most suitable transforming factor related to the daily zonisamide dose ( D ) providing a steady-state serum concentration ( C t) and analyzed the influences of the concomitant use of antiepileptic drugs on C t quantitatively. Data obtained by routine therapeutic drug monitoring from a total of 175 epileptic patients treated with the multiple oral administrations of zonisamide (ZNS) as a powder/tablets, were used for the analysis. Employing the extracellular water volume ( V ECW) as a transforming factor, led the level/dose (L/D) ratio (: C t/( D / V ECW)) to be independent of the patient's age and sex for the administration of ZNS alone. C t was revealed to be dependent on only one variable regarding D / V ECW and expressed as C t=0.604×( D / V ECW). Phenytoin (PHT) significantly lowered ( p <0.01) the L/D ratio to 0.76 of the value for ZNS alone. For a more detailed analysis, we defined the parameter Ri ( i =1, 2, …, 6) as an alteration ratio, representing the influence of each antiepileptic drug on the L/D ratio of ZNS alone. A model based on the assumption that each Ri value was independent from one another and multiplicative, was adopted. The analysis clarified that phenobarbital, valproic acid, carbamazepine, and PHT significantly lowered ( p <0.05) the L/D ratio of ZNS to 0.849, 0.865, 0.846, and 0.804, respectively. In the case of the addition or discontinuance of concomitant treatment with antiepileptic drugs in the same patient, the estimated L/D ratios were calculated using the value of each Ri and compared with the measured ones. The mean of prediction error was calculated as 22.9%. Our results appear valid and Ri should be available for clinical use.
关键词：zonisamide;transforming factor;level/dose ratio;extracellular water volume;concomitant therapy;alteration ratio
