Are phase I studies without drug level determination acceptable?

Summary— Among the main objectives of phase I studies, the definition of the safety profile of the new drug, its pharmacodynamic profile and the relationship between doses, concentrations and effects can be cited. The definition of these correlations is of paramount importance not only for a correct choice of the dose and dosing intervals in patients, but also for a more rational evaluation of the possible risk/benefit ratio at a clinical level. It is hence evident that drug level determination is a "necessary" step during phase I studies in volunteers. These concepts are discussed, with particular emphasis on the possible acceptability of phase I studies without drug level determination.