Since 1999, the Pharmacology Core has supported clinical trials as well as preclinical studies by providing specimen processing and tracking, drug level analyses and pharmacokinetic modeling, and assistance in study design and data interpretation. During the 2000-2003 funding period, the Core developed and offered two new services to clients. One new analytical service is quantifying drug disposition in solid tumors, which was used by the Developmental Therapeutics and Molecular Biology & Human Genetics Programs. Based on this experience, the service is currently being offered for quantifying investigational drug levels in biopsies from clinical trial participants. The second new service is the in vitro evaluation of human safety pharmacology of investigational agents using measurements of adverse drug effects on normal human target cells from dose-limiting tissues. The Core offers an in vitro assay of toxicity to the normal neutrophil progenitor (CFU-GM) in bone marrow, the performance and clinical predictivity of which have been formally validated in a blinded, international study that included the Core as a major participant. This service is an emerging area of increased activity for the Core, having been used by three CCC programs to predict the human safety of nutraceutical-chemotherapy combination regimens being advanced to clinical trials, as well as analog series of novel compounds. With the addition of the new services, the pharmacology Core offers broad, comprehensive pharmacology support in the areas of sample handling, pharmacokinetics, drug-drug interaction, pharmacodynamics, and human safety pharmacology. During the 2000-2003 funding period, the Developmental Therapeutics Program was the major user of pharmacology support services, although all CCC programs used one or more services from this Core. Specimen processing by the Core generated over 17,000 clinical samples for pharmacology studies (over 8,000 from NIH funded clinical trials), of which over 6,000 samples remained in the Core for HPLC and CFU-GM analyses. The Core anticipates that the demand on drug analysis and human safety pharmacology services will shift from pharmaceutical compounds to nutraceuticals and dietary substances that influence the effectiveness of chemotherapy, as well as toward increased emphasis on measurements of small molecule biomarkers.
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