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Variable Expression...
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Lindell, MonicaUppsala universitet,Avdelningen för farmaceutisk biokemi
(author)
Variable Expression of CYP and Pgp Genes in the Human Small Intestine
- Article/chapterEnglish2003
Publisher, publication year, extent ...
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2003-06-06
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Wiley,2003
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-90893
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-90893URI
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https://doi.org/10.1046/j.1365-2362.2003.01154.xDOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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BACKGROUND: The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome p450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes. METHODS: The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed. RESULTS: Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively. CONCLUSIONS: Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large interindividual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation.
Added entries (persons, corporate bodies, meetings, titles ...)
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Karlsson, Mats O.Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Farmakometri(Swepub:uu)matskarl
(author)
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Lennernäs, HansUppsala universitet,Institutionen för farmaci
(author)
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Påhlman, LarsUppsala universitet,Kolorektalkirurgi
(author)
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Lang, Matti A.Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Genreglering
(author)
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Uppsala universitetAvdelningen för farmaceutisk biokemi
(creator_code:org_t)
Related titles
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In:European Journal of Clinical Investigation: Wiley33:6, s. 493-4990014-29721365-2362
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