Abstract
In 25 years, drug metabolism research went from using subcellular particles of undefined content to an understanding of metabolism at the molecular level. The discoveries of cytochrome P450, enzyme induction, reactive intermediates, and genetic polymorphisms were milestones in the field. New publications from the American Society for Pharmacology and Experimental Therapeutics chronicled the discoveries and provided communications to advance the science of drug metabolism.
Footnotes
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↵1 A historical overview of the isolation and identification of the intracellular components of the liver cell is found in the three Nobel Prize lectures of the pioneers in this field, Claude, de Duve, and Palade, which can be found online at http://nobelprize.org/nobel_prizes/medicine/laureates/1974.
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↵2 A recent dedicatory volume honoring Ron Estabrook and his scientific contributions was published in Drug Metabolism Reviews39:251–646, 2007.
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↵3 Gil Mannering has detailed his entrance into the field of drug metabolism and his work with microsomes and metabolism inhibitors in his 1984 Brodie award lecture (Mannering, 1986).
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↵4 Jud Coon discussed how his interest in fatty acid oxidation led him into the world of P450 and studies on the mechanism of P450 catalyzed oxidations in the 1980 Brodie award lecture (Coon, 1981).
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↵5 Anthony Lu has provided an overview of the work leading to solubilization of P450 and an understanding of its role in fatty acid and drug metabolism (Lu, 1998).
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↵6 The collaborative efforts leading to the resolution of rat liver P450s have been described in Wayne Levin's Brodie award lecture (Levin, 1990).
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↵7 Don Jerina was recipient of the third Brodie award. His Brodie lecture details the path from a puzzling retention of radioactivity during p-hydroxylation of p-labeled aromatic rings to the identification of dihydrodiol epoxides as ultimate carcinogenic moieties formed from benzo(a)pyrene and other aromatic hydrocarbons (Jerina, 1983).
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↵8 Paul R. Ortiz de Montellano has detailed the development of this field in his 1994 Brodie lecture (Ortiz de Montellano PR, 1995).
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↵9 Dan Ziegler looks back on the discovery of the flavin monooxygenase system in his Brodie award lecture (Ziegler, 1991).
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.108.021113.
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ABBREVIATIONS: P450, cytochrome P450; 3-MC, 3-methylcholanthrene; HPLC, high-performance liquid chromatography; NMR, nuclear magnetic resonance; GC/MS, gas chromatograph/mass spectrometer; DPH, diphenylhydantoin.
- Received February 18, 2008.
- Accepted February 27, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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The Development of Drug Metabolism Research as Expressed in the Publications of ASPET: Part 2, 1959–1983
