Cancer Pharmacokinetics and Pharmacodynamics Facility

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Abstract: Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF) The UPCI Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF) is nationally recognized for its excellence in developing and delivering PK analyses of investigational agents. Furthermore, during the past grant period the shared resource has built the infrastructure to develop and validate novel pharmacodynamics (PD) methodology to confirm target engagement and determine the extent, duration, and relationship with clinically relevant outcomes of toxicity and/or activity. CPPF activities are based on state-of-the-art quantitative (assays according to FDA guidance for method validation) and qualitative mass spectrometric technologies for small molecules (PK) and quantitative and semi-quantitative analysis for characterization of drug targets (PD) such as enzyme-linked immunosorbent assays (ELISA), immunoblotting, immunohistochemistry (IHC), and quantitative nucleic acid amplification (qPCR). The specific aims of CPPF are to: 1) provide accessible, economical, comprehensive, and state-of-the-art analytical chemical and pharmacokinetic (PK) services in support of basic and clinical UPCI research programs; and 2) provide integrated pharmacodynamic (PD) services in support of translational and clinical UPCI research programs . Working with scientists and clinicians, CPPF (1) provides administrative support for preclinical/clinical protocol submissions, (2) coordinates acquisition and banking of high quality pre-and post-treatment biological samples, (3) identifies and quantitates drugs, metabolites, and other chemical moieties in biological samples, (4) measures serum/plasma cytokines and growth factors, (5) estimates intracellular protein expression (in PBMC, tumor, skin) by various techniques for biomarker development, (6) assists in development of novel detection methodologies for PK and PD, and (7) analyzes the PK-PD relationship within the protocol. The Facility maintains, and continues to expand, a diverse array of analytical chemistry instrumentation operated under accepted practice standards and FDA guidelines for assay implementation and validation. The Co-Directors and key personnel have a combined experience of over 50 years in PK/PD analysis. The provided services are designed to complement existing shared resources in pathology, immunology, and analytical pharmacology with the ultimate goal of advancing clinical/translational research. During the current project period investigators from all 10 UPCI Research Programs used the CPPF.