Factors Influencing the Serum Concentration of Antiepileptic Drugs : Effects of Concomitant Antiepileptic Drugs on the Serum Valproic Acid Concentration in Epileptic Patients
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概要
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The effects of concomitant antiepileptic drugs on the serum valproic acid concentration (C_t) were investigated. Primidone (PRM), phenobarbital (PB), carbamazepine (CBZ), phenytoin (PHT), zonisamide (ZNS), clonazepam (CZP) and ethosuximide (ETS) were coadministrated with valproic acid (VPA). The routine therapeutic drug monitoring data, obtained from epileptic patients who were treated with the repetitive oral administration of the sustained-release preparations of VPA (VPA-R), were used for the analysis. A total of 233 patients were administrated VPA-R alone, and 87, 21 and 6 patients were coadministrated one, two and three different antiepileptic drugs, respectively. Using the data obtained from the patients administrated VPA-R alone, C_t could be expressed conveniently as a function of X as C_t=AX^B. (X : VPA daily dose per modified body weight. A , B : parameter) By comparing the regression line on logC_t vs. logX for VPA-R alone with that for VPA-R plus one concomitant drug, C_t was thus found to be affected at each definite ratio by PB. CBZ, PHT, but not by ZNS. Next, we defined the parameter R_i (i=1, 2,・・・,7) as a coefficient representing the effect of each concomitant antiepileptic drug on C_t. All data were analyzed to estimate R_i, using a model based on the assumption that each R_i Was independent from one another and multiplicative . The analysis clarified that PB. CBZ and PHT lowered C_t to 0.879, 0.812 and 0.833 times, respectively. On the other hand, ZNS did not affect C_t. The number of patients coadministrated PRM, CZP and/or ETS was not sufficient to detect the effect on C_t based on a test of significance.
- 日本医療薬学会の論文
- 1998-12-10
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
Pharmaceutical Division, Kurashiki Central 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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