The Assessment of Pharmacodynamic Effects

Important objectives of the early studies in man, and particularly of volunteer studies, of a putative compound include the generation of data to allow decisions to be made about the further development of the compound. This further development will include studies in patients with the disease for which the compound is targeted with the aim of producing a useful therapeutic agent. The data from early studies in man (Phase I and early Phase II studies) consist of aspects of the pharmacodynamic properties of the compound (what the compound does to man), pharmacokinetic properties (what the body does to the compound) and safety and tolerance. If these aspects of the data generated in early studies suggest that the compound should proceed in development, then early studies should, where possible, provide data on what end-points might be useful in patient studies, what dose and what dosing regimen is sensible to start in patients, and what side-effects should be looked for. Ideally, both pharmacokinetic and pharmacodynamic studies are important in producing data of the kind required for later work. However, in selecting dose and dosing regimens, in particular, pharmacodynamic assessments are especially important. Unfortunately, measurements of pharmacodynamic parameters are not always easy and may require sophisticated and expensive equipment. Considerations of this kind may help to explain the emphasis of the past years on developing pharmacokinetic data rather than dynamic data for new compounds in early studies.