Abstract：
:Cytochrome P450 3A (CYP3A) enzymes metabolize a wide variety of xenobiotics including many drugs. Because CYP3A is localized in both the liver and intestine, it can make a major contribution to the presystemic elimination of substrate drugs after oral administration ('first-pass metabolism'). However, assessments of the relative importance of intestinal versus hepatic CYP3A-mediated first-pass metabolism have been difficult to make and are subject to extensive discussion. To assess systematically the relative contributions of the intestine and liver to first-pass metabolism in vivo, Cyp3a knockout mice expressing human CYP3A4 in the liver or intestine have recently been generated. Analysis of these mice, together with previous observations in humans, substantiates that intestinal CYP3A4 can operate independently of the liver as a highly efficient metabolic barrier during the uptake of various drugs from the intestine. We expect that the insights obtained with these mouse models will contribute to the development of better oral drugs and treatment regimens.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
van Herwaarden AE,van Waterschoot RA,Schinkel AHdoi
10.1016/j.tips.2009.02.003subject
Has Abstractpub_date
2009-05-01 00:00:00pages
223-7issue
5eissn
0165-6147issn
1873-3735pii
S0165-6147(09)00038-8journal_volume
30pub_type
杂志文章abstract：:From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one o...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2010.08.006
更新日期：2010-12-01 00:00:00
abstract：:Parkinson's disease (PD) is a progressive neurodegenerative disorder. Although therapies that treat the symptoms of the disease have proven efficacy, strategies that slow or stop the neurodegenerative process are currently not available. Recently, the National Institute of Neurological Disorders and Stroke (NINDS) con...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2004.03.003
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(93)90064-Q
更新日期：1993-11-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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更新日期：2003-09-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(94)90282-8
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abstract：:Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs predominantly found in microorganisms. Increasing evidence supports a role for TLRs in sterile inflammation as observed in neurodegenerative disorders. This includes work suggesting a contribution for these receptors to t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2006.07.006
更新日期：2006-09-01 00:00:00
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journal_title：Trends in pharmacological sciences
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doi：10.1016/j.tips.2015.05.005
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)88969-5
更新日期：1995-01-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2003.09.010
更新日期：2003-11-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
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doi：10.1016/s0165-6147(99)01342-5
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journal_title：Trends in pharmacological sciences
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journal_title：Trends in pharmacological sciences
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journal_title：Trends in pharmacological sciences
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journal_title：Trends in pharmacological sciences
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journal_title：Trends in pharmacological sciences
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doi：10.1016/s0165-6147(97)01138-3
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abstract：:The histamine H3 receptor was discovered 15 years ago, and many potent and selective H3 receptor agonists and antagonists have since been developed. Currently, much attention is being focused on the therapeutic potential of H3 receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and Henk Timme...
journal_title：Trends in pharmacological sciences
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2006.09.002
更新日期：2006-11-01 00:00:00
abstract：:Transcription factors comprise just over 7% of the human proteome and serve as gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated cell signaling pathways converge on transcription facto...
journal_title：Trends in pharmacological sciences
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abstract：:During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.02.008
更新日期：2016-05-01 00:00:00
