Summary
Drug metabolism input to the discovery process has been to date largely on an empirical case by case basis. Considerable advances have been made, such that basic rules can be applied to the behaviour of a compound in man based on physico-chemistry and structure. This is particularly true in the area of the cytochrome P-450 enzymes, the principal enzymes involved in the primary clearance of drugs. The major human forms, CYP2D6, CYP2C9 and CYP3A4 all have distinct substrate preferences which are being catalogued and rationalised. Such understandings will not only impact on existing drugs. Since the enzymes and systems will remain the same, these understandings can be applied to the design of molecules for the targets of the future, whilst the structure activity relationships of those targets are being researched and revealed.
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Smith, D.A. Design of drugs through a consideration of drug metabolism and pharmacokinetics. Eur. J. Drug Metab. Pharmacokinet. 19, 193–199 (1994). https://doi.org/10.1007/BF03188921
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DOI: https://doi.org/10.1007/BF03188921