Evaluation of Carbamazepine Pharmacokinetic Profiles in Mice with Kainic Acid-Induced Acute Seizures(Miscellaneous)
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概要
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The purpose of the present study was to evaluate the effect of kainic acid (KA)-induced acute seizures on the pharmacokinetic profiles of antiepileptic drug, carbamazepine (CBZ) in mice. Experimental acute seizure in mice was induced by intraperitoneal injection of KA (30mg/kg), and mice were provided for experiments after 48h of KA treatment. The portal plasma concentrations of CBZ and its metabolite carbamazepine-10,11-epoxide (CBZ-epo) had trends to decrease as compared to the control mice, whereas the brain CBZ and CBZ-epo concentrations was actually lower in KA treated mice. On the other hand, the exsorption of CBZ from blood to the intestinal lumen via P-glycoprotein (P-gp) in KA treated-mice was significantly increased in parallel with that of Rhodamine-123 (Rho123), a P-gp substrate. Western blotting analysis for intestinal and cerebral P-gp showed that the P-gp expression was induced in the KA-treated mice. The apparent brain-to-plasma concentration ratio (Kp) of CBZ in the KA-treated mice showed significant decrease but that of CBZ-epo did not. Moreover, in the KA-treated mice, the percentage of protein binding was significantly increased, and found to be an inverse proportion in the relationship between the Kp and protein binding of CBZ. In conclusion, the mechanism responsible for a decreased brain CBZ concentration in the KA-induced seizure mice is based on the up-regulation of P-gp function in tissues and plasma protein binding of CBZ.
- 公益社団法人日本薬学会の論文
- 2008-12-01
著者
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SUGIOKA Nobuyuki
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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TAKADA Kanji
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Nishimura Asako
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Womens College of Liber
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Shibata Nobuhito
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Womens College of Liber
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Honda Naoki
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Takada Kanji
Dep. Of Pharmacokinetics Kyoto Pharmaceutical Univ.
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Takada K
Department Of Biopharmaceutics Kyoto Pharmaceutical University:exploratory Development Laboratories
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Nishimura A
同志社女子大学 薬学部生物薬剤学
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Takada Kanji
Department Of Biopharmaceutics Kyoto Pharmaceutical University:exploratory Development Laboratories
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Nishimura Asako
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Doshisha Women's College Of L
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Sugioka Nobuyuki
Dep. Of Pharmacokinetics Kyoto Pharmaceutical Univ.
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Takada K
Kyoto Pharmaceutical Univ. Kyoto Jpn
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Shibata Nobuhito
Dep. Of Pharmacokinetics Kyoto Pharmaceutical Univ.
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Shibata Nobuhito
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts
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