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Drug Metabolism and Disposition Fast Forward
First published on March 10, 2008; DOI: 10.1124/dmd.107.019687

0090-9556/08/3606-1039-1045$20.00
DMD 36:1039-1045, 2008

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Characterization of Cytochrome P450 Protein Expression along the Entire Length of the Intestine of Male and Female Rats

Doreen Mitschke, Andreas Reichel, Gert Fricker, and Ursula Moenning

Research Pharmacokinetics, Bayer Schering Pharma AG, Berlin, Germany (D.M., A.R., U.M.); and Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany (G.F.)

Intestinal cytochrome P450 (P450) proteins play an important role in the biotransformation of drugs and may significantly limit their oral absorption and bioavailability. Therefore, we have investigated the amount of P450 proteins via Western blot analysis along the entire intestine of male and female rats. Despite of the use of an inbred rat strain, controlled housing conditions for the animals, and a timed sample preparation, high interindividual differences in the expression of all P450 proteins was observed. CYP3A (135–243 fmol/mg of protein) and CYP2B1 (107–645 fmol/mg of protein) were the most abundant P450 isoforms in the duodenum and jejunum of rat intestine but were present in neither the ileum nor the colon. Compared with CYP2B1 and CYP3A, CYP2D1 (25–71 fmol/mg of protein) and CYP2C6 (3–10 fmol/mg of protein) were only expressed in minor amounts. CYP2C11 could not be identified in the entire rat intestine. In conclusion, this is the first systematic evaluation and quantification of the expression of P450 proteins along the entire length of the intestine in both male and female rats. These data will provide a basis for a better understanding of the extent of intestinal metabolism along the gastrointestinal tract.

Address correspondence to: Dr. Doreen Mitschke, Bayer Schering Pharma Ag, FPK, Muellerstr. 178, 13353 Berlin, Germany. E-mail: doreen.mitschke{at}bayerhealthcare.com




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Closing the Gaps: A Full Scan of the Intestinal Expression of P-Glycoprotein, Breast Cancer Resistance Protein, and Multidrug Resistance-Associated Protein 2 in Male and Female Rats
Drug Metab. Dispos., July 1, 2008; 36(7): 1249 - 1254.
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