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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M3 - Article
C2 - 9699650
AN - SCOPUS:0032145499
VL - 58
SP - 3248
EP - 3253
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 15
ER -