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  • Title: Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human alpha1-acid glycoprotein.
    Author: Fuse E, Tanii H, Kurata N, Kobayashi H, Shimada Y, Tamura T, Sasaki Y, Tanigawara Y, Lush RD, Headlee D, Figg WD, Arbuck SG, Senderowicz AM, Sausville EA, Akinaga S, Kuwabara T, Kobayashi S.
    Journal: Cancer Res; 1998 Aug 01; 58(15):3248-53. PubMed ID: 9699650.
    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.
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