During the previous funding period, the pharmacology core laboratory has supported all three projects, providing measurement of more than a dozen different anticancer drugs. In the previous application the specific aims outlined pharmacology studies with hexamethylene bisacetamide; leucovorin, 5 fluorouracil, and 5 fluoro-2'-deoxyuridine; lometrexol; chloroquinoxaline sulfonamide(CQS), and trimetrexate. Each of these assays was developed and pharmacology studies completed. The analytical laboratory performed drug concentration analysis on more than 2000 samples annually. The contribution of the pharmacology core to the clinical development of all trans retinoic acid, suramin, and CQS have been particularly important.
The specific aims for the pharmacology core laboratory will be: 1. To continue analytical support for ongoing studies of (CQS), edatrexate, taxol, and all trans retinoic acid (ATRA); 2. Assays for phenylacetic acid, phenylbutyric acid and phenyl acetylglutamine; 3. Develop a method for lobaplatin in human body fluids; 4. Develop assays for clinically important retinoids including All trans retinoic acid, 9-cis retinoic acid, 13 cis reinoic acid and novel retinoids proposed in Project 1; 5. Establish a method for measuring the P 450 test substrate, erythromycin, in plasma; 6. Develop a more sensitive HPLC assay which can specifically separate and quantitate antifolates including methotrexate, edatrexate, trimetrexate and newer antifols; 7. To employ capillary electrophoresis to develop a micro assay for methotrexate polyglutamates in small tissue samples.
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