The primary focus of this project is always on the application of pharmacokinetic principles to questions of relevance to the treatment of cancer. The emphasis upon specific disease targets changes somewhat, as do the classes of drugs under investigation. There is a continuing shift from extracellular pharmacology to the use of intracellular measurements. Over the last year, specific areas of interest included: 1. Clinical pharmacokinetic studies have been completed for suramin and are nearly finished for azidothymidine. Work continues on the matching of in vitro and in vivo exposure conditions and on efforts to describe the intracellular pharmacology of azidothymidine. 2. Although the total resources expended in Phase I trials are smaller than in other phases of drug development, these trials are an important milestone in the clinical pharmacology of anticancer drugs. The Blood Level Working Group is focusing specifically on the interface between preclinical and clinical studies. 3. A joint clinical trial has been activated with the Radiation Oncology Branch for the combined delivery of iododeoxyuridine and fluorodeoxyuridine. In addition to plasma pharmacokinetics, DNA from peripheral granulocytes will be studied for indications of biochemical modulation.
