Changes in Digoxin Pharmacokinetics Treated with Lipopolysaccharide in Wistar Rats(Biopharmacy)
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概要
- 論文の詳細を見る
Lipopolysaccharide (LPS) is a highly bioactive substance that can cause local as well as systemic damage to various organs of both humans and animals, even at very low doses. However, there are a few reports on drug pharmacokinetics during endotoxemia. In this study, we analyzed the pharmacokinetics of digoxin (a therapeutic agent for cardiac insufficiency) as a probe drug for a two-compartment model in a rat model of endotoxemia induced by LPS for 5 d. Digoxin was given to Wistar rats intravenously (i.v.), orally (p.o.), and intra-intestinally using an in situ closed-loop method (loop). The AUC_<i.v.> was significantly increased in the LPS (+) group through- out the experiment (p<0.05). There was significant decrease in V_2 (volume of distribution of tissue compartment) on Day 1-3 (p<0.05). On Day 1-2 after LPS administration, the AUC_<p.o.> was significantly increased in the LPS (+) group (p<0.05). The AUC_<loop> was significantly increased throughout the experiment (p<0.05). The elimination rate constant was unchanged. Thus LPS administration affected the absorption but not the excretion of digoxin. The findings of this study suggest that digoxin absorption increased and the volume of distribution of tissue compartment decreased after LPS administration (5 mg/kg, i.p.). It appears that digoxin pharmacokinetics recover over 3 d after LPS administration.
- 社団法人日本薬学会の論文
- 2008-06-01
著者
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Kato Ryuji
Department Of Clinical Pharmacology & Pharmacokinetics Osaka University Of Pharmaceutical Scienc
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Kawai Takako
Laboratory Of Clinical Pharmacy And Clinical Pharmacokinetics Osaka University Of Pharmaceutical Sci
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KATO Ryuji
Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sc
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TSUKURA Yuri
Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sc
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AMANO Fumio
Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences
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HIROTANI Yoshihiko
Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University
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IJIRI Yoshio
Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sc
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TANAKA Kazuhiko
Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sc
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FUJIWARA Azusa
Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sc
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MORIGUCHI Jun
Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sc
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NAKAGAWA Machiko
Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sc
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UCHIDA Kagehiro
Biomarker Science Co., Ltd.
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Uchida Kagehiro
Biomarker Science Co. Ltd.
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Tsukura Yuri
大阪薬科大学 臨床薬剤学研究室
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Tsukura Yuri
Laboratory Of Clinical Pharmacy And Clinical Pharmacokinetics Osaka University Of Pharmaceutical Sci
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Tsukura Yuri
Department Of Clinical Pharmacy And Clinical Pharmacokinetics Osaka University Of Pharmaceutical Sci
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Moriguchi Jun
Laboratory Of Clinical Pharmacy And Clinical Pharmacokinetics Osaka University Of Pharmaceutical Sci
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Kato Ryuji
新潟薬科大学 薬学部
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Tokunaga Yuka
大阪薬科大学 臨床薬剤学研究室
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Nakagawa Machiko
Laboratory Of Clinical Pharmacy And Clinical Pharmacokinetics Osaka University Of Pharmaceutical Sci
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Ijiri Yoshio
大阪薬科大学 臨床薬剤学研究室
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Ijiri Yoshio
Laboratory Of Clinical Pharmacy And Clinical Pharmacokinetics Osaka University Of Pharmaceutical Sci
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Fujiwara Azusa
Laboratory Of Clinical Pharmacy And Clinical Pharmacokinetics Osaka University Of Pharmaceutical Sci
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Amano Fumio
大阪薬科大学 臨床薬剤学研究室
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Amano Fumio
Laboratory Of Biodefense And Regulation Osaka University Of Pharmaceutical Sciences
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Amano Fumio
Laboratory Of Biodefense & Regulation Osaka University Of Pharmaceutical Sciences
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Hirotani Yoshihiko
Laboratory Of Clinical Pharmaceutics Faculty Of Pharmacy Osaka Ohtani University
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Hirotani Yoshihiko
大阪薬科大学 臨床薬剤学研究室
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Ijiri Yoshio
Department Of Clinical Pharmacy And Clinical Pharmacokinetics Osaka University Of Pharmaceutical Sci
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Tanaka Kazuhiko
Department Of Clinical Pharmacology & Pharmacokinetics Osaka University Of Pharmaceutical Scienc
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Hirotani Yoshihiko
大阪大谷大学 薬学部臨床薬剤学
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