Search

The field of clinical pharmacology is the discipline engaged in optimal drug discovery, development, and use, based on an in-depth knowledge of human pharmacology and therapeutics. Although many think clinical pharmacology is simply the study of pharmacokinetics, pharmacodynamics, and pharmacogenetics, the role of the clinical pharmacologists covers all avenues of drug discovery, development, therapeutics, optimal drug therapy, and education. This expanded understanding is important as we start to address the overwhelming mandate and the unfortunate shortage of qualified investigators in the field (both physicians and non-physicians). [ABSTRACT FROM AUTHOR]

UCN-01 is a protein kinase inhibitor under development as a novel anticancer drug. The initial pharmacologic features in patients were not predicted from preclinical experiments. The distribution volume and the systemic clearance were much lower than those in experimental animals (mice, rats, and dogs), and the elimination half-life was unusually long (>200 hours). The unbound fraction in human plasma was also much smaller than that in dogs, rats and mice, as was the binding of UCN-01 to human alpha-1 acid glycoprotein much stronger than that to human serum albumin or human gamma-globulin. The association constants for alpha-1 acid glycoprotein and human plasma were approximately 8 x 10(8)(mol/L)(-1), indicating extremely high affinity. In this review article, the authors discuss the pharmacologic features of UCN-01 across species and provide a perspective on how this information could be applied prospectively to the future development of this agent. [ABSTRACT FROM AUTHOR]