title: Developing drug prototypes: pharmacology replaces safety and tolerability?
abstract: New medicines are designed to bind to receptors or enzymes and are tested in animal cells, tissues and whole organisms in a highly scientific process. Subsequently they are often administered to human subjects with tolerability as the primary objective. The process of development is considered to be linear and consecutive and passes through the famous four phases of development (Phase I-Phase IV). This is efficient for those projects for which the uncertainty about the development is low. There is, however, an increasing number of new prototypical compounds resulting from the increased biological knowledge with a high level of uncertainty. For these prototypical drugs development has to proceed in a much more adaptive manner, using tailor-made objectives, the development of special methodology and a cyclical rather than a linear type of project management.
authors.affiliation: Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. ac@chdr.nl
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cohen
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000009:adverse effects / Q000639:trends; D055808:Drug Discovery / Q000639:trends*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D020714:Maximum Tolerated Dose; D010601:Pharmacology, Clinical / Q000639:trends*; D014481:United States; D014486:United States Food and Drug Administration / Q000639:trends