Pharmacokinetic and Pharmacodynamic Analysis of the Antihypercalcemic Effect of Incadronate Disodium in Rats
スポンサーリンク
概要
- 論文の詳細を見る
Incadronate concentrates into the bone as a target organ after intravenous administration of incadronate disodium. Mature osteoclasts has take up incadronate from the bone surface and convert it from an active to an inactive form. As a result, incadronate decreases the plasma calcium concentration by suppressing bone resorption. In this study, the pharmacokinetic and pharmacodynamic (PK/PD) analysis model for ascertaining the antihypercalcemic effects of incadronate disodium was developed in rats. Data on both the concentration of incadronate in bone and that of free calcium in blood after intravenous administration from our previous study were used for analysis. To estimate the concentration in the surface layer of bone, data on the concentration of incadronate in bone after single intravenous administration were analyzed based on the PK model considering three-compartments. The estimated concentrations in the surface layer in bone were applied to the PD model as an input function. The PD model was developed to analyze the changes in the plasma calcium concentration after a single intravenous administration considering an irreversible inhibition of osteoclast activity. The obtained fitted curves were in good agreement with the observed data. The model could explain the long duration of the antihypercalcemic effect of incadronate disodium and should be useful for planning rational dose regimens for effective antihypercalcemic therapy.
- 公益社団法人日本薬学会の論文
- 2001-11-01
著者
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SATO Hitoshi
Department of Clinical and Molecular Pharmacokinetics/Pharmacodynamics, School of Pharmaceutical Sci
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YAMADA Yasuhiko
Department of Mathematics, Faculty of Science, Kobe University
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OHNO Yoshiyuki
Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Gradu
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SAWADA Yasufumi
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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IGA Tatsuji
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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Ohno Yoshiyuki
Department Of Pharmacy University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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OHTANI Hisakazu
Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
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SAWADA Yasufumi
Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
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Sawada Y
Department Of Pharmaceutics Graduate School Of Pharmacertical Sciences Kyushu University
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Sawada Yasufumi
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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Takahashi Katsuhiko
Department of Physiological Chemistry, School of Pharmaceutical Sciences, Showa University
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TAKAHASHI KOICHIRO
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical
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IGA Tatsuji
International University of Health and Welfare
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Yamada Yasuhiko
Department Of Clinical Evaluation Of Drug Efficacy School Of Pharmacy Tokyo University Of Pharmacy A
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Yamada Yasuhiko
Department Of Pharmacy University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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Takahashi Katsuhiko
Department Of Physiological Chemistry School Of Pharmaceutical Sciences Showa University
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Sato H
Department Of Pharmacy University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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Sato Hitoshi
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Usui Takashi
Drug Metabolism Laboratories Drug Development Division Yamanouchi Pharmaceutical Co. Ltd.
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Usui Takashi
Institute For Drug Development Research Yamanouchi Pharmaceutical Co. Ltd.
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Iga T
Department Of Pharmacy University Of Tokyo Hospital
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Iga Tatsuji
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Tsuchiya F
Department Of Pharmacy University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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Tsuchiya Fumito
Hospital Pharmacy Ichihara Hospital Teikyo University
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TSUCHIYA Fumito
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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OHTANI Hisakazu
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University
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Takahashi K
Department Of Physiological Chemistry School Of Pharmaceutical Sciences Showa University
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Iga T
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Yamada Yasuhiko
Department Of Clinical Evaluation Of Drug Efficacy School Of Pharmacy Tokyo University Of Pharmacy A
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Tsuchiya Fumito
Department Of Pharmacy University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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Ohno Yoshiyuki
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine The University Of Tokyo
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Ohno Yoshiyuki
Department Of Pharmacy Kinjogakuin University
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Yamada Yasuhiko
Department Of Clinical Evaluation Of Drug Efficacy School Of Pharmacy Tokyo University Of Pharmacy A
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Ohtani Hisakazu
Laboratory Of Drug Informatics Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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Takahashi Koichiro
Institute For Drug Discovery Research Yamanouchi Pharmaceutical
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Sato Hitoshi
Department Of Cardiology Juntendo University School Of Medicine
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SATO Hitoshi
Department of Animal Science, Faculty of Agriculture, Tohoku University
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