Advantage of Extracellular Water Volume for the Relation between Serum Carbamazepine Concentration and Transformed Daily Dose
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概要
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We concluded a study to clarify the most suitable factors related to the carbamazepine daily dose (D) with the serum concentration (C_t). Therapeutic drug monitoring data obtained from epileptic patients who were chronically treated with single and repetitive oral administrations of carbamazepine (CBZ). The 119 steadystate data were used. First, when the extracelluler water volume (V_<ECW>) was employed as a transforming factor, C_t/(D/V_<ECW>) ratio was found to be independent of the patient's age. In addition, a multiple regression analysis revealed that C_t was dependent on only D/V_<ECW>. Form these findings, we concluded that C_t could only be related with D/V_<ECW>. Next, a 1-compartment model including two assumptions that CBZ binds to plasma protein and the distribution volume of free-CBZ is proportional to V_<ECW>, was postulated for our analysis. At steady-state, C_t was expressed as follows : C_t = 1αX(1+K_aC_<bs>+αK_aX)/(1+αK_aX) (X = D/V_<ECW>. α, K_a, C_<bs> : parameter) The parameter values were estimated by the nonlinear least square method as α , K_a and C_<bs> were 0.013, 1.6 and 12.8 respectively. The plasma protein binding ratios were 92.3, 90.2 and 87.1(%) when the serum CBZ concentrations were 6,8 and 10[μg/mL], respectively. These values closely corrected with those reported previously. As a result, V_<ECW> is considered to be a suitable transforming factor for the relation between C_t and D, and our model seems to be approriate.
- 日本医療薬学会の論文
- 2000-04-10
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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