The Research Center for Clinical Pharmacology and Drug Toxicology consists of clinical pharmacologists in Medicine, Pediatrics and Psychiatry working in association with a nucleus of investigators whose research in biochemical pharmacology includes the biotransformation of drugs, analytical pharmacology and pharmacokinetics. The scientific resources in the Center will enable application of the best available techniques and approaches to studies of drugs in man and provide an environment for training investigators in clinical pharmacology. The research program will focus on the metabolism, distribution and biochemical effects of drugs in man. Within this framework, attention will be given to the delineation of interactions between drugs in patients and to the development of knowledge that will enable prediction of toxicity. The relevance of the marked interindividual differences in the plasma levels of certain drugs to their efficacy and toxicity will be investigated as well as the influence of disease processes and age on patients' response to drugs. A further related aim will be the development of analytical techniques for accurately measuring nanogram amounts of drugs and metabolites in body fluids, including approaches such as selected-ion-monitoring with the mass spectrometer and improved application of high pressure liquid chromatography. The clinical pharmacology of drugs for the treatment of cardiac arrhythmias and hypertension will be studied, including an investigation of the relative safety of different antihypertensive drugs. The pharmacology of the prostaglandins and thromboxanes and their relation to disease processes is under investigation with emphasis on the role of thromboxanes in pathologic spasm of coronary and cerebral arteries, the clinical phamacology of anti-inflammatory drugs used in arthritis, the regulation of platelet aggregation and the development of quantitative methods for measuring thromboxane formation in man. The biotransformation of drugs to active and inactive metabolites as well as their distribution, transport, binding and biochemical effects in a variety of species will be investigated in an attempt to provide a rational basis for the prediction of their effects and toxicity in man.