遺伝子組換えヒト組織性Ｐｌａｓｍｉｎｏｇｅｎ　Ａｃｔｉｖａｔｏｒ（ｒｔ‐ＰＡ）誘導体（Ｅ６０１０）の体内動態に関する研究（１）　ラットに｀１２５´Ｉ‐標識Ｅ６０１０を単回静脈投与した時の血中濃度推移，分布，代謝および排せつの｀１２５´Ｉ‐標識ｒｔ‐ＰＡとの比較検討

• 水尾 均

  エーザイ株式会社 筑波研究所

• 世古 隆之

  エーザイ株式会社 筑波研究所

• 野瀬 浩一

  エーザイ株式会社 筑波研究所

• 安藤 智美

  エーザイ株式会社 筑波研究所

• 影井 佳子

  エーザイ株式会社 筑波研究所

• 菊池 きよ美

  エーザイ株式会社 筑波研究所

• 三島 万年

  エーザイ株式会社 筑波研究所

• 上田 正隆

  エーザイ株式会社 筑波研究所

• 中田 宏

  エーザイ株式会社 筑波研究所

• 堀江 透

  エーザイ株式会社 筑波研究所

• 杠 輝昭

  エーザイ株式会社 筑波研究所

書誌事項

タイトル別名

• Studies on the Metabolic Fate of Modified Recombinant Tissue-Type Plasminogen Activator (E6010) (1): Blood or Plasma Concentration, Distribution, Metabolism and Excretion in Rats after a Single Intravenous Administration of l25I-E6010 in Comparison with l25I-Recombinant Tissue-Type Plasminogen Activator (rt-PA).

抄録

Blood or plasma concentration, distribution, metabolism and excretion of E6010 were studied in male rats after a single intravenous administration of ¹²⁵I-E6010 in comparison with ¹²⁵I-rt-PA.<BR> 1. After a single intravenous administration of ¹²⁵I-E6010, plasma clearances of TCA-precipitable radioactivity, immunoreactivity, fibrinolytic activity and the unchanged E6010 were 10.3, 11.2, 3.1 and 5.5 times lower than those after dosing of ¹²⁵I-rt-PA, respectively.<BR> In the plasma, the complexes of ¹²⁵I-E6010 with α₂-macroglobulin and with α₂-plasmin inhibitor were observed after dosing of ¹²⁵I-E6010, as well as after dosing of ¹²⁵I-rt-PA.<BR> 2. After a single intravenous administration of ¹²⁵I-E6010, liver levels of TCA-precipitable radioactivity reached maximum level at 15 min after administration accounting for about 19% of administered radioactivity. In the case of ¹²⁵I-rt-PA, it reached maximum level at 5 min accounting for about 54% of administered dose. These results suggest that the differences in the distribution to the liver between E6010 and rt-PA resulted in the difference of plasma clearances.<BR> 3. Within 7days after a single int ravenous administration of ¹²⁵I-E6010, 96.05% and 5.32% of the administered radioactivity were excreted into urine and feces, respectively. Biliary excretion of radioactivity was 17.01% of the dose within 48hr after a single intravenous administration of ¹²⁵I-E6010. Both radioactivity excreted in urine and in bile consisted almost of small molecular weight metabolites or free ¹²⁵I.

収録刊行物

• 薬物動態

  薬物動態 11 (6), 556-584, 1996

  日本薬物動態学会

キーワード

• Modified plasminogen activator
• E6010
• rt-PA
• Plasma level
• Tissue distribution
• Metabolism
• Excretion
• Single intravenous administration
• Rats

詳細情報

• CRID: 1390282679646013696
• NII論文ID: 10007374015
• NII書誌ID: AN10144117
• DOI: 10.2133/dmpk.11.556
• ISSN: 09161139
• Web Site: http://www.jstage.jst.go.jp/article/dmpk1986/11/6/11_6_556/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1997166773
• 本文言語コード: ja
• 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