Pharmacological screening of new chemical entities in human subjects and methods of data handling.

摘要

1 A system is described for screening new chemical entities in normal human subjects, which is designed to search for novel drug actions at an early stage of drug development. 2 In single (subject) blind experiments, doses are increased incrementally from one subject to next, with immediate feed-back of results from each dose. 3 As many physiological variables as possible are recorded, for which a purpose-designed apparatus system was constructed, and connected to a computer. 4 To overcome problems of inter-subject variability, the need for sensitivity, and to identify drug-related effects from the mass of data generated, a novel data management system was developed, and physiological profiles of volunteer subjects were built up to provide control data. 5 Results from a validation experiment in which isoprenaline was infused intravenously at different rates are presented and discussed.