RT Journal Article
SR Electronic
T1 Molecular and Physical Mechanisms of First-Pass Extraction
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 161
OP 166
VO 27
IS 2
A1 Stephen D. Hall
A1 Kenneth E. Thummel
A1 Paul B. Watkins
A1 Kenneth S. Lown
A1 Leslie Z. Benet
A1 Mary F. Paine
A1 Robert R. Mayo
A1 D. Kim Turgeon
A1 David G. Bailey
A1 Robert J. Fontana
A1 Steven A. Wrighton
YR 1999
UL http://dmd.aspetjournals.org/content/27/2/161.abstract
AB This is a report of a symposium held at the March 1997 meeting of the American Society for Pharmacology and Therapeutics in San Diego. Our understanding of the events that control first-pass drug elimination in humans has increased tremendously by two sequential discoveries. First, cytochrome P-450s 3A4 and 5 are expressed at high concentrations in both hepatocytes and upper intestinal enterocytes, and therefore limit the systemic availability of many drugs. Second, P-glycoprotein is expressed at the lumenal surface of the intestinal epithelium and therefore also acts to oppose the absorption of unchanged drug. The following discussion brings together our current understandings of these interrelated phenomena to aid a more complete picture of how they may contribute both qualitatively and quantitatively to first-pass elimination. The American Society for Pharmacology and Experimental Therapeutics