PHARMACOLOGY SHARED RESOURCE (Core-529) ABSTRACT Overview: An important component of drug-based studies is the assessment of drug exposure in both preclinical and clinical studies. The Pharmacology Shared Resource (PharmSR) provides a mechanism by which University of Colorado Cancer Center (UCCC) investigators can plan and carry out pharmacokinetic (PK) and pharmacodynamic (PD) studies in consultation with expert investigators. Equipment: Quantitative analytical methods offered include high performance liquid chromatography (HPLC) with UV/Vis and fluorescent detection, LC tandem mass spectrometry (LC/MS/MS), and other biochemical analysis methods (e.g. ELISA, enzymatic). Institutional support led to the purchase of an AB SCIEX QTRAP? 6500 LC/MS/MS system during the last funding period, providing state of the art technology to UCCC investigators. Services: Services offered by the PharmSR include: (1) consultation on PK study design; (2) development, validation and implementation of appropriate analytical assays for drugs in biological fluids and tissues; and (3) PK and PD modeling and mathematical analysis of analytical data. PK modeling services include systems based approaches (non- compartmental modeling), compartmental modeling, Physiologically-Based PK analyses (PBPK) and population approaches. Consultation and Education: The PharmSR provides consultation to help members with limited pharmacology or PK background to design appropriate experiments and analyze PK data. Consultations provided to members roughly equates to approximately 5 letters of support being requested annually for grant submission proposing use of the PharmSR. Management: The PharmSR is located at CSU and is an institutional core jointly managed by the UCCC and CSU. CCSG funding represents 24% of the annual operating budget. The remaining support comes from the CCTSI grant (13%) and user fees (63%). PharmSR is overseen by the Associate Director of Translational Research. Use of Services: Since July 2011, 55 investigators have used the PharmSR services. Thirty-six percent (20) were UCCC members representing four of the six UCCC programs and generating 20 peer-reviewed publications. Future Directions: The Pharm SR is currently establishing multiplex assays to directly quantitate panels of ATP-binding cassette (ABC) transporter proteins and drug metabolizing enzymes (P450s) from in vitro, preclinical and patient specimens. The goal is for the PharmSR to offer these focused proteomic assays to quantitate proteins relevant to drug development and mechanism of action.
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