Preclinical Guidelines for the Testing of New Drugs: Pharmacodynamic Aspects
In No. 563 of WHO’s Technical Report Series, “Guidelines for Evaluation of Drugs for Use in Man,”1 it is stated that preclinical “pharmacodynamic studies should be designed to demonstrate the expected therapeutic effect of the drug and, wherever practicable, its mechanism.” In many cases it is difficult, if not impossible, to comply with that request, especially with respect to the mechanism of action of many of the drugs in use, often for a long time, for which we do not know precisely how and where they act. Furthermore, problems may arise in planning experimental studies to show probable therapeutic effect because such experimental models either do not exist or are inadequate and do not allow us to draw conclusions about what may happen in man. Of course, each new chemical entity will be studied by appropriate in-vitro methods as well as in acute experiments in animals, to establish its pharmacodynamic profile. However, the pharmacological features of a new chemical give only limited information about its therapeutic usefulness. Despite the fact that the species of man does not differ fundamentally from various animal species with respect to pharmacodynamic responses, and that, consequently, human pharmacology resembles animal pharmacology, the therapeutic potential of a new substance cannot simply be derived from the pharmacodynamic effects demonstrable in acute studies.
KeywordsChemical Entity Pharmacodynamic Study Pharmacodynamic Profile Acute Experiment Therapeutic Usefulness
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