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.
Publication types
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Clinical Trial
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Comparative Study
MeSH terms
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Adult
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Alkaloids / pharmacokinetics
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Alkaloids / pharmacology*
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Alkaloids / toxicity
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Animals
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / toxicity
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Blood Proteins / metabolism
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Chromatography, High Pressure Liquid
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Dogs
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / toxicity
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Humans
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Infusions, Intravenous
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Mice
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Mice, Nude
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Protein Binding
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Protein Kinase C / antagonists & inhibitors*
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Rats
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Staurosporine / analogs & derivatives
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Transplantation, Heterologous / immunology
Substances
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Alkaloids
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Antineoplastic Agents
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Blood Proteins
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Enzyme Inhibitors
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7-hydroxystaurosporine
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Protein Kinase C
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Staurosporine