タルチレリン水和物の体内動態　（３）　　ラットにおける脳内動態

• 児玉 裕彦

  田辺製薬株式会社 医薬開発研究所

• 福島 健

  田辺製薬株式会社 医薬開発研究所

• 千島 進

  田辺製薬株式会社 医薬開発研究所

• 杉原 重孝

  田辺製薬株式会社 医薬開発研究所

• 吉川 正美

  田辺製薬株式会社 医薬開発研究所

書誌事項

タイトル別名

• Disposition of Taltirelin. (3): The Transfer into the Brain and Brain Distribution in Rats.

抄録

The transfer, distribution and degradation of taltirelin in the brain were investigated after oral (3 mg/kg) or intravenous (1 mg/kg) administration and injection into cisterna cerebellomedullaris (300 μg/kg) in rats.<BR> 1. Taltirelin was hardly degraded for 3 hr in blood, whereas TRH was degraded with a half-life of 5.4 min. Taltirelin and TRH were degraded by the brain homogenate with half-lives of 64.4 and 7.9 min, respectively, suggesting that taltirelin is 8 times more stable than TRH in the brain. In the cerebrospinal fluid taltirelin and TRH were equally stable for 3 hr.<BR> 2. Concentration of unchanged taltirelin in the brain decreased more slowly with a half-lives of 55.4 ?? 65.7 min than that in the blood (t_1/2 : 23.1 min) after intravenous administration of taltirelin. After oral administration, the brain concentrations of unchanged taltirelin reached the maximum levels of 135 ?? 364 pg/g and then decreased slowly. The unchanged taltirelin was not detected in the brain at 6 hr after dosing.<BR> 3. After injection of ¹⁴C-taltirelin into cisterna cerebellomedullaris, the brain concentrations of radioactivity reached the maximum levels of 2.3 ?? 5.5 μg eq./g at 1 hr after injection and then decreased slowly. These results indicated that taltirelin was transferred from cerebrospinal fluid into the brain, in which taltirelin was retained for a long time.<BR> 4. After intravenous adm inistration of ¹⁴C-taltirelin or ³H-TRH, there is a difference in the brain distribution of radioactivity between taltirelin and TRH. Radioactive concentration in pituitary gland, which was target organ of hormonic effect, at 5 min after intravenous administration of ¹⁴C-taltirelin was 1/10 of that after dosing of ³H-TRH.

収録刊行物

• 薬物動態

  薬物動態 12 (5), 483-490, 1997

  日本薬物動態学会

キーワード

• Taltirelin
• TRH
• Stability
• Brain distribution
• Injection into cisterna cerebellomedullaris
• Rat

詳細情報

• CRID: 1390001204670202496
• NII論文ID: 10007531280
• NII書誌ID: AN10144117
• DOI: 10.2133/dmpk.12.483
• ISSN: 09161139
• Web Site: http://www.jstage.jst.go.jp/article/dmpk1986/12/5/12_5_483/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1998088409
• 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