The first priority in characterizing the pharmacokinetics of an agent is to have a reliable and reproducible analytical method for quantitating agents in biological fluids and tissues. Our research efforts have been devoted to the development of agents that specifically target the aberrant biology of neoplasms, e.g., altered signal transduction pathways, inhibition of angiogenesis, or binding of peptide growth factors involved in the genesis of the malignant phenotype. The successful development of such compounds requires extensive use of pharmacokinetic and pharmacodynamic concepts. In addition, determining the concentration of these agents in tissue or plasma is of the utmost importance in correlating efficacy or toxicity. This differs from the development of standard cytotoxic agents in which myelosuppression is the predominate complication noted and concentration analysis is not emphasized. Within the Clinical Pharmacokinetics Section (CPS), HPLC is often utilized to develop analytical methods. We use state of the art equipment to support our translational pharmacokinetic/ pharmacodynamic research. This includes several Liquid Chromatograph systems equipped with photo diode array detectors which are controlled by HP Chemstation software (run on pentium computers), as well as precision fluorescence, LC-MSD (mass spectroscopy detector), and electrochemical detectors. We also utilize GC techniques and collaborate with laboratories that have NMR and AAS instruments. In some cases, ELISA and RIA are the preferred method of quantification. The CPS has developed analytical methods for monitoring TNP-470, phenylacetate, phenylbutyrate, tamoxifen, UCN-01, CAI, thalidomide, COL-3 and coenzyme Q10. Furthermore, we are also quantitating suramin, paclitaxel, melphalan, docetaxel, vinblastine, perifosine, SU5416 and AZT from biological fluids. The laboratory is also working in collaboration on the development of two RIA assay methods: PSC 833 and ricin immunotoxins (CD19 and CD22). Lastly, the CPS is active in measuring plasma concentrations of numerous cytokines and growth factors by ELISA (VEGF, bFGF, TGFb, TNF, MMP2, MMP9).
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