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

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 μM. However, concentrations 10-fold greater are well tolerated in humans, and the compound has a markedly prolonged T( 1/4 ). Specific binding to human α₁-acidic glycoprotein has been demonstrated. These findings reinforce the need to consider actual clinical pharmacology data in 'real time' with phase I studies.