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
em 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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Orosomucoide
/
Alcaloides
/
Antineoplásicos
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Japão