Pharmacokinetics

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Designated as a developing resource in January 2005, the Pharmacokinetics/ Pharmacodynamics (PK/PD) Resource is a new CCSG Resource. Its mission is to support clinical and preclinical drug development at RPCI by providing quality analytical data using sensitive methods for PK/PD studies of cancer therapeutic and preventive agents with quality assurance, cost effectiveness and necessary modeling support. It also provides small molecule quantification for investigators. The Resource is organized into two sections: the Clinical/Preclinical Drug Development directed by Lakshmi Pendyala, PhD, and the Steroid Hormone and Vitamin D Section directed by Josephia Muindi, MD, PhD. Technical personnel consist of a Mass Spectrometrist, 1.5 FTE research associates and two technicians. The Resource provides: 1) consultation and input for PK/PD studies for protocol, CTEP/LOI and grant preparations; 2) development and validation of analytical assays for new small molecules; 3) extraction of drugs/ metabolites from biological matrices and analysis by using LC/MS/MS, UPLC, HPLC, Atomic Absorption; 4) real-time qRT-PCR gene expression assays for PD end points; and 5) PK data analysis. Large instrumentation in the Resource consists of two LC/MS/MS instruments, two HPLCs, one UPLC, an Atomic Absorption Spectrophotometer and a real-time qRT-PCR instrument. Small-molecular quantification includes several antimetabolites, taxanes, topoisomerase targeted agents, anthracyclines, Vitamin-D/metabolites, targeted agents (sunitinib) and other molecules such as tryptophan, kyurenine and novobiocin. Elemental analysis includes selenium, platinum and gold. The Resource is guided by a Steering Committee and operates on Institute support and chargebacks. Future plans for the Resource are to attract a larger peer-review-funded CCSG program user base, provide expanded support to Phase I/I I studies, expand the technical staff and add a fluorescence detector to the UPLC system. The Resource is used by all six Programs and 65% of users are CCSG members. $49,410 in CCSG support is requested, representing 9% of the total operating budget.