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

Research output: Contribution to journalArticlepeer-review

206 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3248-3253
Number of pages6
JournalCancer Research
Issue number15
Publication statusPublished - 1998 Aug 1
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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