Abstract
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.
Footnotes
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↵1 To whom requests for reprints should be addressed, at Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko, Kogyo Co., Ltd., 1188, Shimotogari, Nagaizumi-Cho, Sunto-Gun, Shizuoka 411, Japan. Phone: 81-559-89-2021; Fax: 81-559-86-7430; E-mail: takashi.kuwabara@kyowa.co.jp.
- Received March 27, 1998.
- Accepted June 15, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 15
