Influence of Coadministered Antiepileptic Drugs on Serum Zonisamide Concentrations in Epileptic Patients : Quantitative Analysis Based on Suitable Transforming Factor (Biopharmacy)
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概要
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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_1) and analyzed the influences of the concomitant use of antiepileptic drugs on C_1 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_1/(D/V_<ECW>)) to be independent of the patient's age and sex for the administration of ZNS alone. C_1 was revealed to be dependent on only one variable regarding D/V_<ECW> and expressed as C_1= 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 R_i (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 R_i 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 R_i and compared with the measured ones. The mean of prediction error was calculated as 22.9%. Our results appear valid and R_i should be available for clinical use.
- 公益社団法人日本薬学会の論文
- 2003-12-01
著者
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MORITA Shushi
Department of Pharmacy
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Kimura M
Pharmaceutical Division Kurashiki Central Hospital
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Kimura Michio
Research Center Of Neurological Disease Kansai College Of Oriental Medicine
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Morita S
Kagawa Medical Univ. Kagawa Jpn
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Morita Shushi
Department Of Hospital Pharmacy Kagawa University
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Kimura Michio
Pharmaceutical Division Kurashiki Central Hospital
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森田 清司
Tokushima Research Institute Otsuka Pharmaceutical Co. Ltd.
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FUKUOKA Noriyasu
Department of Hospital Pharmacy, Kagawa University
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TSUKAMOTO Toyohisa
Department of Hospital Pharmacy, Kagawa University
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UNO Junji
Department of Hospital Pharmacy, Okehazama Hospital
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Uno Junji
Department Of Hospital Pharmacy Okehazama Hospital
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Tsukamoto T
Department Of Hospital Pharmacy Kagawa University
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Tsukamoto Toyohisa
Department Of Hospital Pharmacy Kagawa Medical School
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Fukuoka Noriyasu
Department Of Hospital Pharmacy Kagawa Medical School
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