Characterization of CS-023 (R04908463), a novel parenteral carbapenem antibiotic, and meropenem as substrates of human renal transporters

• SHIBAYAMA Takahiro

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

• SUGIYAMA Daisuke

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

• KAMIYAMA Emi

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

• TOKUI Taro

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

• HIROTA Takashi

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

• IKEDA Toshihiko

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

書誌事項

タイトル別名

• Characterization of CS-023 (RO4908463), a Novel Parenteral Carbapenem Antibiotic, and Meropenem as Substrates of Human Renal Transporters

抄録

  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 K_m value of the hOAT3-mediated transport was 847 μM, and the uptake was inhibited by probenecid, p-aminohippurate and benzylpenicillin with K_i 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

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 22 (1), 41-47, 2007

  日本薬物動態学会

キーワード

• organic anion transporters
• carbapenem antibiotics
• renal tubular secretion
• CS-023 (RO4908463)
• meropenem

詳細情報

• CRID: 1390001205179149824
• NII論文ID: 10018732973
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.22.41
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715302317?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715302317?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2007232884
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可