Probenecid: Its Chromatographic Determination, Plasma Protein Binding, and in vivo Pharmacokinetics in Dogs
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概要
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Pharmacokinetics (PK) of probenecid including plasma probenecid concentrations, in vitro plasma protein binding properties, and in vivo PK parameters were determined in dogs. Probenecid concentrations were best determined by HPLC, which showed good linearity and good recovery with simple plasma preparation. The quantification limit of probenecid was approximately 50 ng/ml at S/N ratio = 3, by simple procedure with HCl and methanol treatment. Probenecid showed two types of binding characteristics, i.e., high-affinity with low-capacity and low-affinity with high-capacity binding. This result indicated 80-88% of probenecid was bound to plasma protein(s) at observed concentrations (< 80 μg/ml) in vivo at an intravenous dose of 20 mg/kg. Plasma probenecid concentration-time profile following i.v. administration in dogs showed biphasic decline and well fitted a two-compartment open model. The total body clearance was 0.34 ± 0.04 ml/min/kg, volume of distribution at steady-state was 0.46 ± 0.07 l/kg, elimination half-life was 18 ± 6 hr, and mean residence time (MRT) was 23 ± 6 hr. Since probenecid has been known as a potent inhibitor of renal tubular excretion of acidic drugs and highly binds to plasma proteins, our observation in relation to plasma protein binding and PK parameters will serve as the basic information concerning drug-drug interactions in dogs and in other mammalian species.
- 公益社団法人 日本獣医学会の論文
著者
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Ito Nobuhiko
Laboratory Of Veterinary Radiology And Radiation Biology Department Of Veterinary Medicine Kitasato
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Kakizaki Takehiko
Laboratory Of Veterinary Radiology And Radiation Biology Department Of Veterinary Medicine Kitasato
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KUBO Satoshi
Laboratory of Wood Chemistry, Graduate School of Agriculture, Hokkaido University
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Natsuhori Masahiro
Laboratory Of Veterinary Radiology And Radiation Biology Department Of Veterinary Medicine Kitasato
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KAKIZAKI Takehiko
Laboratory of Veterinary Radiology and Radiation Biology Kitasato University, School of Veterinary Medicine and Animal Sciences
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YOKOYAMA Yukiko
Laboratory of Veterinary Radiology and Radiation Biology Kitasato University, School of Veterinary Medicine and Animal Sciences
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KARASAWA Azusa
Laboratory of Veterinary Radiology and Radiation Biology Kitasato University, School of Veterinary Medicine and Animal Sciences
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YAMADA Naoaki
Laboratory of Veterinary Radiology and Radiation Biology Kitasato University, School of Veterinary Medicine and Animal Sciences
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KUBO Satoshi
Laboratory of Veterinary Radiology and Radiation Biology Kitasato University, School of Veterinary Medicine and Animal Sciences
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ITO Nobuhiko
Laboratory of Veterinary Radiology and Radiation Biology Kitasato University, School of Veterinary Medicine and Animal Sciences
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NATSUHORI Masahiro
Laboratory of Veterinary Radiology and Radiation Biology Kitasato University, School of Veterinary Medicine and Animal Sciences
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