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 oar peptide growth factors involved in the genesis of the malignant phenotype. The successful development of such agents requires extensive use of pharmacokinetic and pharmacodynamic concepts. 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. Consequently, the concentrations of these compounds in tissue and plasma are important for activity. Within the Clinical Pharmacokinetic 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, phenylacetylglutamine, tamoxifen and, UCN- 01. Furthermore, we are also assaying coenzyme Q10, suramin, thalidomide CAI, paclitaxel, 9-AC, melphalan, amphoteracin B and AZT by previously published methods. The CPB is working in collaboration on the development of two RIA assay methods: PSC-833 as well as both the CD19 and CD22 directed immunotoxins. The CPS is also active in measuring plasma concentrations of numerous cytokines and growth factors by ELISA. In collaboration with other sections the CPS monitors the plasma concentrations for other agents in clinical development (flavopiridol, cisplatin IP, carboplatin IP, PMEA, ormaplatin, and gallium).
