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.
| Original language | English |
|---|---|
| Pages (from-to) | 3248-3253 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 58 |
| Issue number | 15 |
| Publication status | Published - 1998 Aug 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human α1-acid glycoprotein. / Fuse, Eiichi; Tanii, Hiromi; Kurata, Noriaki; Kobayashi, Hiroyuki; Shimada, Yasuhiro; Tamura, Tomohide; Sasaki, Yasutsuna; Tanigawara, Yusuke; Lush, Richard D.; Headlee, Donna; Figg, William D.; Arbuck, Susan G.; Senderowicz, Adrian M.; Sausville, Edward A.; Akinaga, Shiro; Kuwabara, Takashi; Kobayashi, Satoshi.
In: Cancer Research, Vol. 58, No. 15, 01.08.1998, p. 3248-3253.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human α1-acid glycoprotein
AU - Fuse, Eiichi
AU - Tanii, Hiromi
AU - Kurata, Noriaki
AU - Kobayashi, Hiroyuki
AU - Shimada, Yasuhiro
AU - Tamura, Tomohide
AU - Sasaki, Yasutsuna
AU - Tanigawara, Yusuke
AU - Lush, Richard D.
AU - Headlee, Donna
AU - Figg, William D.
AU - Arbuck, Susan G.
AU - Senderowicz, Adrian M.
AU - Sausville, Edward A.
AU - Akinaga, Shiro
AU - Kuwabara, Takashi
AU - Kobayashi, Satoshi
PY - 1998/8/1
Y1 - 1998/8/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0032145499&partnerID=8YFLogxK
M3 - Article
C2 - 9699650
AN - SCOPUS:0032145499
VL - 58
SP - 3248
EP - 3253
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 15
ER -