Pharmacology for Chemists: Drug Discovery in Context
12: Predicting Dose and Selective Efficacy in Clinical Studies from Preclinical Experiments: Practical Pharmacodynamics
Published:25 Oct 2017
Special Collection: RSC eTextbook CollectionProduct Type: Textbooks
R. G. Hill, in Pharmacology for Chemists: Drug Discovery in Context, ed. R. Hill, T. Kenakin, and T. Blackburn, The Royal Society of Chemistry, 2017, pp. 483-503.
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Animal pharmacology experiments to establish putative efficacy and to predict dose in subsequent human subject investigations have been, and continue to be, an important part of the drug discovery process. The predictive value of such animal work is sometimes minimal and this chapter reviews the reasons for this and suggests ways in which the most robust data can be obtained. The use of chiral molecules to obtain data that is reliably associated with the pharmacological target and the use of surrogate endpoints are considered. The problem of species differences in pharmacology is dealt with in the context of neuropharmacological studies of the role of substance P. The importance of imaging studies and ways in which reproducibility can be improved are also briefly considered.