Pharmacokinetic Modeling and Prediction of Plasma Pyrrole-Imidazole Polyamide Concentration in Rats Using Simultaneous Urinary and Biliary Excretion Data
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概要
- 論文の詳細を見る
The use of urinary and/or biliary excretion data was considered as an alternative approach if the bioanalytical method lacked the appropriate sensitivity to adequately characterize the serum or plasma concentration–time profile. This approach is used for the analysis of plasma concentration–time profile under the lower limit of quantification (LLOQ) of various analytical instruments. The objective of this study was to develop a pharmacokinetic (PK) model that describes the plasma concentration–time profiles under LLOQ of HPLC using urinary and biliary excretion data. As model compounds, pyrrole (Py)-imidazole (Im) polyamides 1035 (MW, 1035.12) and 1666 (MW, 1665.78) were used. The cumulative urinary excretions of Py-Im polyamides 1035 and 1666 were 72.4±11.6 and 4.8±0.5% of the administered dose, respectively. The cumulative biliary excretion of Py-Im polyamide 1035 was 4.3±0.4% of the administered dose, and Py-Im polyamide 1666 was not detected. The plasma concentration–time profiles of Py-Im polyamide 1035 were adequately described using linear and non-linear output compartments. The developed PK model could be used to describe the plasma concentration profiles using the linear output compartment interpreted as the urine compartment and the non-linear output compartment interpreted as the bile compartment. This PK model will be able to provide a more accurate prediction of the plasma concentration profiles under LLOQ.
著者
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Ueno Takahiro
Division Of Nephrology Hypertension And Endocrinology Department Of Medicine Nihon University School
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Fukuda Noboru
Advanced Res. Inst. For The Sci. And Humanities Nihon Univ.
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Sugiyama Hiroshi
Department of Chemistry, Graduate School of Science Kyoto University
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AOYAMA Takahiko
Department of Clinical Pharmacokinetics, College of Pharmacy, Nihon University
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Aoyama Takahiko
Department Of Cardiac Surgery Aichi Medical University
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Aoyama Takahiko
Dep. Of Clinical Pharmacokinetics School Of Pharmacy Nihon Univ.
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Matsumoto Yoshiaki
Department Of Clinical Pharmacology And Toxicology Showa Pharmaceutical University
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Nagashima Takashi
Department Of Obstetrics And Gynecology School Of Medicine Keio University
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NAGASE Hiroki
Advanced Research Institute for the Science and Humanities, Nihon University
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Fukasawa Akiko
Department Of Clinical Pharmacokinetics College Of Pharmacy Nihon University
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Yokoe Tsubasa
Department of Clinical Pharmacokinetics, College of Pharmacy, Nihon University
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Sugiyama Hiroshi
Department Of Chemistry Graduate School Of Science Kyoto University
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Matsumoto Yoshiaki
Department Of Clinical Pharmacokinetics College Of Pharmacy Nihon University
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Nagashima Takashi
Department Of Clinical Pharmacokinetics College Of Pharmacy Nihon University
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Nagashima Takashi
Department Of Applied Physics Faculty Of Science Tokyo University Of Education:(present Address) Tok
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Sugiyama Hiroshi
Department Of Chemistry Faculty Of Science
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Sugiyama Hiroshi
Department of Chemistry, Graduate School of Science, Kyoto University
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NAGASHIMA Takashi
Department of Clinical Pharmacokinetics, College of Pharmacy, Nihon University
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Fukuda Noboru
Advanced Research Institute for the Science and Humanities, Nihon University
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Ueno Takahiro
Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine
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