The Clinical Pharmacology Branch (CPB) as a whole is devoted to the development of agents that specifically target the aberrant biology of neoplasms, e .g., altered signal transduction pathways or peptide growth factors involved in the genesis of the malignant phenotype. The successful development of such agents requires the use of pharmacokinetic and pharmacodynamic concepts to a greater extent than that of cytotoxic agents. Each interaction of a cytotoxic drug with its target results in damage, so it is not surprising that oncologists typically are only required to consider the dose of these drugs. This theory fails with drugs that interact with their targets or receptors in a reversible manner. The effects of such drugs parallel receptor occupancy, and, by extension, the concentrations of these compounds in tissue and plasma are significant for activity. Within the Clinical Pharmacokinetics Section (CPS) we have the following analytical capabilities; five high performance liquid chromatographs utilizing electrochemical, UV absorbance, and fluorescence detection; one gas chromatograph utilizing flame ionization and nitrogen-phosphorus detection; and one TDX fluorescence immunoassay. The CPS has developed analytical methods for monitoring plasma concentrations of TNP-470, phenylacetate, phenylbutyrate and phenylacetylglutamine. Furthermore, we are also assaying coenzyme QlO, suramin, and AZT by previously published methods.
