Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human α1-acid glycoprotein

Eiichi Fuse, Hiromi Tanii, Noriaki Kurata, Hiroyuki Kobayashi, Yasuhiro Shimada, Tomohide Tamura, Yasutsuna Sasaki, Yusuke Tanigawara, Richard D. Lush, Donna Headlee, William D. Figg, Susan G. Arbuck, Adrian M. Senderowicz, Edward A. Sausville, Shiro Akinaga, Takashi Kuwabara, Satoshi Kobayashi

研究成果: Article査読

200 被引用数 (Scopus)

抄録

The pharmacokinetics of UCN-01 after administration as a 72- or 3-h infusion to cancer patients in initial Phase I trials displayed distinctive features that could not have been predicted from preclinical data. The distribution volumes (0.0796-0.158 liters/kg) and the systemic clearance (0.0407-0.252 ml/h/kg) were extremely low, in contrast to large distribution volume and rapid systemic clearance in experimental animals. The elimination half-lives (253-1660 h) were unusually long. In vitro protein binding experiments demonstrated that UCN-01 was strongly bound to human α1-acid glycoprotein. The results suggest that unusual pharmacokinetics of UCN-01 in humans could be due, at least in part, to its specifically high binding to α1-acid glycoprotein.

本文言語English
ページ(範囲)3248-3253
ページ数6
ジャーナルCancer Research
58
15
出版ステータスPublished - 1998 8月 1
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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