| Literature DB >> 9699650 |
E Fuse1, H Tanii, N Kurata, H Kobayashi, Y Shimada, T Tamura, Y Sasaki, Y Tanigawara, R D Lush, D Headlee, W D Figg, S G Arbuck, A M Senderowicz, E A Sausville, S Akinaga, T Kuwabara, S Kobayashi.
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 alpha1-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 alpha1-acid glycoprotein.Entities:
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Year: 1998 PMID： 9699650
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701