Empirical Approach for Improved Estimation of Unbound Serum Concentrations of Valproic Acid in Epileptic Infants by Considering Their Physical Development
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概要
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The unbound serum concentration of valproic acid (VPA) is closely related to its therapeutic efficacy. In epileptic infants, the unbound VPA concentration varies largely from patient to patient, being difficult to predict using the reported equations for older children. To establish an equation to estimate the unbound concentration in infants, we empirically characterized the relationship between total and unbound VPA concentrations, taking their growth and development into consideration. Data were retrospectively collected from archived clinical records of 30 epileptic infants aged 0—11 months old. The relationship between total and unbound VPA concentrations was analyzed according to the Langmuir equation, in which the patients body weight, height, and body surface area were considered as physical development indices. Inter- and intra-individual variabilities in the VPA concentrations were also considered. It was shown that the unbound VPA concentration in infants is properly estimated when their body weights are taken into account, in which the parameter for the maximum binding site concentration (Bm) increases as the body weight increases, while that for the dissociation constant (Kd) is unaltered. Additionally, the relationship was shown to slightly change when the infants are concomitantly treated with VPA and the other antiepileptics. These findings provide useful information to adjust the VPA dosage to achieve optimal therapeutic efficacy in epileptic infants.
著者
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Sendo Toshiaki
Department Of Hospital Pharmacy Okayama University Medical And Dental School
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OHTSUKA Yoko
Department of Child Neurology, Okayama University Graduate School of Medicine and Dentistry
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Sendo Toshiaki
Department Of Hospital Pharmacy Faculty Of Medicine Kyushu University
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Ueshima Satoshi
Department of Hospital Pharmacy, Okayama University Hospital
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Aiba Tetsuya
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Sato Tomoaki
Department of Hospital Pharmacy, Okayama University Hospital
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Matsunaga Hisashi
Department of Hospital Pharmacy, Okayama University Hospital
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Kurosaki Yuji
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Aiba Tetsuya
Graduate School Of Medicine Dentistry And Pharmaceutical Sciences Okayama Univ.
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Ohtsuka Yoko
Department Of Child Neurology Okayama University Graduate School Of Medicine And Dentistry
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Kurosaki Yuji
Graduate School Of Medicine Dentistry And Pharmaceutical Sciences Okayama University
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Sato Tomoaki
Department Of Applied Pharmacology Kagoshima University Graduate School Of Medical And Dental Scienc
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Ohtsuka Yoko
Department Of Child Neourology Okayama University Medical School
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Sendo Toshiaki
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Sendo Toshiaki
Department of Hospital Pharmacy, Okayama University Hospital
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Ohtsuka Yoko
Department of Child Neurology, Okayama University Hospital
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