The Handbook of Medicinal Chemistry
Chapter 7: Drug Metabolism
Published:03 Feb 2023
R. Lock, P. J. H. Webborn, C. W. Vose, and R. M. J. Ings, in The Handbook of Medicinal Chemistry, ed. S. E. Ward and A. Davis, The Royal Society of Chemistry, 2023, ch. 7, pp. 265-297.
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It is almost impossible to design a bioavailable, long half-life and safe drug without a good understanding of both the principles of, and specific risks associated with, drug metabolism. Designing potent compounds with limited metabolic liabilities has proven to be one of the key challenges of drug discovery. The reasons for this, and some potential solutions, are explored in this chapter. The issues described also include the propensity for rapid metabolism, the risks associated with reactive metabolites and the origins of metabolically derived drug–drug interactions. The factors influencing the metabolism of drugs, the challenges of adopting prodrug strategies and exploiting active metabolites are also discussed, as are the complexities of metabolism–transport interplay. The chapter aims to provide a good understanding of drug metabolism and its relevance and value in support of drug research and development.