Pharmacologic agents are powerful tools for research in the biology of aging and the pathophysiology of age- related disease. A pharmacologic approach to study aging offers a number of experimental advantages including flexibility regarding the beginning and end of an intervention, the ability to combine a drug with other interventions, and the capacity to treat any animal including genetically modified models. Further, the potential to move a drug between laboratory animal models into human studies provides a solid basis of the translational relevance of the work. Consequently, the demand to develop and test potential aging-modulating compounds has increased substantially in the last 5-10 years. To meet these needs, we created the Analytical Pharmacology Core in 2015. The overall goal of this Core ? which is unique among all Nathan Shock Centers ? is to promote the application of existing and novel drugs to studies of aging and age-related diseases. This goal is achieved through the following Specific Aims:
Specific Aim 1 : Assist investigators by developing dosage forms that effectively deliver drugs to specific mechanistic targets in animal models of aging (e.g. mice, rats, and marmosets) at UTHSCSA and other institutions. The Core assists investigators through the following services: a) Developing and validating bioanalytical assays for drugs and small molecules; b) Designing and creating usable, effective dosage forms; c) Measuring and confirming concentrations and stability of drugs in dosage forms; and d) Quantifying and confirming drug concentrations in blood and tissues.
Specific Aim 2 : Provide consultation and education regarding experimental design, data interpretation, and grant/manuscript writing for investigators using drugs in aging research. Specific areas of expertise include: a) Informing on the process of dosage form development; b) Recommending pharmacologic approaches, such as level/timing of doses in studies; c) Proposing and justifying pharmacokinetic experiments, as needed; and d) Assisting in interpretation of data and preparation of papers and grants. During the current funding period, the Analytical Pharmacology Core measured levels of 21 different compounds in laboratory animal food and biospecimens (tissues, plasma, urine) for 23 laboratories across the U.S. that conduct investigations related to aging biology. For the new funding period, we have incorporated leading-edge HPLC/MS/MS systems that have significantly enhanced assay sensitivity, halved new bioanalytical assay development and service turnaround time, and doubled productivity. Another innovative feature for the next funding period is the incorporation of a procedure with dried blood spots that allows collection of multiple tail blood samples from rodents during single-dose pharmacokinetic experiments. This method will be particularly useful because it lowers supply costs, eliminates the need for freezer storage, provides drug stability, reduces the numbers of animals (especially mice), and avoids the need to sacrifice them.
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