Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human alpha1-acid glycoprotein.
Cancer Res
; 58(15): 3248-53, 1998 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Orosomucoid
/
Alkaloids
/
Antineoplastic Agents
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cancer Res
Year:
1998
Type:
Article
Affiliation country:
Japan