Clinical pharmacology of UCN-01: initial observations and comparison to preclinical models.

Abstract:

:UCN-01 (7-hydroxystaurosporine; NSC 638850) is a protein kinase antagonist selected for clinical trial based in part on evidence of efficacy in a preclinical renal carcinoma xenograft model. Schedule studies and in vitro studies suggested that a 72-h continuous infusion would be appropriate. In rats and dogs, maximum tolerated doses produced peak plasma concentrations of approximately 0.2-0.3 microM. However, concentrations 10-fold greater are well tolerated in humans, and the compound has a markedly prolonged T1/2. Specific binding to human alpha1-acidic glycoprotein has been demonstrated. These findings reinforce the need to consider actual clinical pharmacology data in "real time" with phase I studies.

authors

Sausville EA,Lush RD,Headlee D,Smith AC,Figg WD,Arbuck SG,Senderowicz AM,Fuse E,Tanii H,Kuwabara T,Kobayashi S

doi

10.1007/s002800051080

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

S54-9

eissn

0344-5704

issn

1432-0843

journal_volume

42 Suppl

pub_type

临床试验,杂志文章
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