Characterization of CS-023 (R04908463), a novel parenteral carbapenem antibiotic, and meropenem as substrates of human renal transporters
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- SHIBAYAMA Takahiro
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
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- SUGIYAMA Daisuke
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
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- KAMIYAMA Emi
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
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- TOKUI Taro
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
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- HIROTA Takashi
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
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- IKEDA Toshihiko
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
書誌事項
- タイトル別名
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- Characterization of CS-023 (RO4908463), a Novel Parenteral Carbapenem Antibiotic, and Meropenem as Substrates of Human Renal Transporters
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To characterize the renal handling of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, and meropenem in humans, we examined their affinities as substrates to human renal transporters. In vitro studies on the uptake of [14C]CS-023 and [14C]meropenem were conducted using HEK293 cells expressing human organic anion transporters (hOAT) 1, hOAT3, hOAT4, and the human organic cation transporters (hOCT) 1 and hOCT2. CS-023 did not serve as the substrate for any of the transporters tested. On the other hand, meropenem was transported by hOAT1 and hOAT3. The Km value of the hOAT3-mediated transport was 847 μM, and the uptake was inhibited by probenecid, p-aminohippurate and benzylpenicillin with Ki values of 3.76, 712, and 202 μM, respectively. One of the reasons why CS-023 is not a substrate of hOATs, and vice versa for meropenem, would be that a very small proportion of CS-023 exists as the anionic form at the physiological pH, whereas 50% of meropenem exists as the anionic form. These findings indicate that the lack of recognition of CS-023 by renal transporters is one of the reasons for its long plasma half-life in humans compared with meropenem which undergoes renal tubular secretion mediated by hOAT1 and hOAT3.<br>
収録刊行物
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 22 (1), 41-47, 2007
日本薬物動態学会
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詳細情報 詳細情報について
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- CRID
- 1390001205179149824
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- NII論文ID
- 10018732973
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- NII書誌ID
- AA1162652X
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- ISSN
- 18800920
- 13474367
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- 本文言語コード
- en
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- データソース種別
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- JaLC
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- 抄録ライセンスフラグ
- 使用不可