We conducted a study to clarify the most suitable transforming factor related to the daily zonisamide dose (
D) providing a steady-state serum concentration (
Ct) and analyzed the influences of the concomitant use of antiepileptic drugs on
Ct 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 (
VECW) as a transforming factor, led the level/dose (L/D) ratio (:
Ct/(
D/
VECW)) to be independent of the patient's age and sex for the administration of ZNS alone.
Ct was revealed to be dependent on only one variable regarding
D/
VECW and expressed as
Ct=0.604×(
D/
VECW). 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.
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