Abstract
The dramatic changes in drug metabolism research in the last 25 years are well documented in the publications of the American Society for Pharmacology and Experimental Therapeutics (ASPET). New analytical tools combined with modern molecular biological techniques have provided unprecedented access to the workings of the cell. A field that concentrated on only a handful of primary enzymes now has a list of hundreds in its purview. Genetic variation, environmental impact, and molecular diversity have all come under study in attempts to follow the fate of drugs and chemicals. Examples from ASPET journals will be used to illustrate the dramatic advancements in the field.
Footnotes
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↵1 John Fenn received the Nobel Prize in 2002. His lecture on the development of the electrospray interface is an excellent overview of this remarkable field (http://nobelprize.org/nobel_prizes/chemistry/laureates/2002/fenn-lecture.html).
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↵2 Drag Anders was awarded the 1999 Brodie Award in recognition of his contributions to the field over a 35-year period starting with studies on SKF 525-A inhibition of drug metabolism (Anders and Mannering, 1966).
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↵3 Tom Poulos was the recipient of the 2004 Brodie Award. His Brodie lecture provides an excellent history of the crystal structure of P450 and a detailed comparison to nitric oxide synthase (Poulos, 2005).
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↵4 Dan Nebert received the Brodie Award in 1986 for his many contributions to the field. His award lecture details how an initial finding of a difference in inducibility between mouse strains led to the discovery of the Ah receptor and shaped his future career (Nebert, 1988).
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↵5 Frank Gonzalez, in accepting the 2006 Brodie Award, discussed the progress in our understanding of CYP2E1 and particularly the value of the 2E1 knockout mouse in elaborating the physiological functions of the enzyme (Gonzalez, 2007).
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↵6 Eric Johnson, in his acceptance of the 2002 Brodie Award, detailed the wealth of information gained from the crystal structure of CYP2C5 (Johnson, 2003).
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↵7 Bettie Sue Siler Masters, who was involved in many of the pioneering studies on this reductase, received the 2000 Brodie Award. A retrospective of her studies of P450 reductase and nitric oxide synthase has been published (Masters, 2005).
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↵8 Curt Klaassen was awarded the 2008 Brodie Award in honor of his many outstanding contributions to our understanding of the role of metabolism in toxicity.
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↵9 Grant Wilkinson, one of the authors of the fexofenadine study, was a pioneer in pharmacokinetics who passed away in 2006. Grant was an active member of ASPET, and his many contributions to the field are memorialized in an article in Clin Pharmacol Ther (Wood, 2006).
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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.108.023226.
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ABBREVIATIONS: P450, cytochrome P450; HPLC, high-performance liquid chromatography; UPLC, ultra-performance liquid chromatography; GC/MS, gas chromatograph/mass spectrometer; MS/MS, tandem mass spectrometers; LC/NMR, liquid chromatograph/nuclear magnetic resonance; LC/MS, liquid chromatograph/mass spectrometer; CAR, constitutive androstane receptor; PXR, pregnane X receptor.
- Received July 2, 2008.
- Accepted July 14, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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