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British Journal of Pharmacology (2006) 147, S89–S99. doi:10.1038/sj.bjp.0706466

Drug metabolism and pharmacogenetics: the British contribution to fields of international significance

John Caldwell1

1Faculty of Medicine, The University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA

Correspondence: John Caldwell, E-mail: jcc@liv.ac.uk

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Abstract

The branch of pharmacology we now call 'drug metabolism', the consideration of the enzymes and procesess determining the disposition of drugs in the body, emerged in the 1840s on the continent of Europe, but British science made little or no contribution until the 1920s. From this point on, the development of the field through the 20th century was shaped to a very significant extent by a series of influential British workers, whose contributions were of global significance and who can now be seen as fathers of the subject. Since the 1950s, and gaining pace inexorably from the 1970s, the significance of drug metabolism to human therapeutics has been greatly added to by the emergence of pharmacogenetics, clinically important hereditary variation in response to drugs, which underpins the current emphasis on personalised medicine. This review examines the British contributions to both these fields through the lives of seven key contributors and attempts to place their work both in the context of its time and its lasting influence.

Keywords:

Drug metabolism, pharmacogenetics, Boyland, Dutton, Garrod, Gowland Hopkins, Price Evans, Smith, Williams, glucuronic acid conjugation, glutathione conjugation, acetylation polymorphism, CYP2D6 polymorphism

Abbreviations:

CYP, cytochrome P450; FMO, microsomal flavin-containing mono-oxygenase; ICI, Imperial Chemical Industries; NMR, nuclear magnetic resonance; TMA, trimethylamine; TMAO, trimethylamine N-oxide; UDP, uridine diphosphate; UDPGA, uridine 5'-diphosphoglucuronic acid

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