Unpredicted Clinical Pharmacology of UCN-01 Caused by Specific Binding to Human α1-Acid Glycoprotein
E Fuse, H Tanii, N Kurata, H Kobayashi, Y Shimada… - Cancer Research, 1998 - AACR
E Fuse, H Tanii, N Kurata, H Kobayashi, Y Shimada, T Tamura, Y Sasaki, Y Tanigawara…
Cancer Research, 1998•AACRThe 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 …
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 …
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.
AACR
