Unusually Low Clearance of Two CYP3A Substrates, Alprazolam and Trazodone, in a Volunteer Subject with Wild‐Type CYP3A4 Promoter Region
A healthy 40‐year‐old Caucasian male volunteer displayed unusually low clearance and long elimination half‐life of alprazolam and trazodone, two CYP3A substrate drugs, following single‐dose oral administration in clinical pharmacokinetic studies. Genomic DNA isolated from the individual's perip...
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| Veröffentlicht in: | Journal of clinical pharmacology 2000-02, Vol.40 (2), p.200-204 |
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| container_title | Journal of clinical pharmacology |
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| creator | Moltke, Lisa L. Tran, Thanh Huu Cotreau, Monette M. Greenblatt, David J. |
| description | A healthy 40‐year‐old Caucasian male volunteer displayed unusually low clearance and long elimination half‐life of alprazolam and trazodone, two CYP3A substrate drugs, following single‐dose oral administration in clinical pharmacokinetic studies. Genomic DNA isolated from the individual's peripheral blood was subjected to polymerase chain reaction amplification and subsequent sequence analysis of a 592 base‐pair segment upstream from the CYP3A coding region. The analysis revealed no variation from wild‐type in the nucleotide present at position −290, previously suggested to influence expression and/or activity of CYP3A. The functional significance of this promoter region mutation is unclear and requires further evaluation. |
| doi_str_mv | 10.1177/00912700022008748 |
| format | Article |
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Genomic DNA isolated from the individual's peripheral blood was subjected to polymerase chain reaction amplification and subsequent sequence analysis of a 592 base‐pair segment upstream from the CYP3A coding region. The analysis revealed no variation from wild‐type in the nucleotide present at position −290, previously suggested to influence expression and/or activity of CYP3A. 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Drug treatments ; Promoter Regions, Genetic ; Trazodone - pharmacokinetics</subject><ispartof>Journal of clinical pharmacology, 2000-02, Vol.40 (2), p.200-204</ispartof><rights>2000 American College of Clinical Pharmacology</rights><rights>2000 SAGE Publications</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4182-4b8cea43eca2cceb3c3520e9db2a01c3c2d3d0ee090fc4bf18c613ec1247ac393</citedby><cites>FETCH-LOGICAL-c4182-4b8cea43eca2cceb3c3520e9db2a01c3c2d3d0ee090fc4bf18c613ec1247ac393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1177%2F00912700022008748$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1177%2F00912700022008748$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1250015$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10664927$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moltke, Lisa L.</creatorcontrib><creatorcontrib>Tran, Thanh Huu</creatorcontrib><creatorcontrib>Cotreau, Monette M.</creatorcontrib><creatorcontrib>Greenblatt, David J.</creatorcontrib><title>Unusually Low Clearance of Two CYP3A Substrates, Alprazolam and Trazodone, in a Volunteer Subject with Wild‐Type CYP3A4 Promoter Region</title><title>Journal of clinical pharmacology</title><addtitle>J Clin Pharmacol</addtitle><description>A healthy 40‐year‐old Caucasian male volunteer displayed unusually low clearance and long elimination half‐life of alprazolam and trazodone, two CYP3A substrate drugs, following single‐dose oral administration in clinical pharmacokinetic studies. Genomic DNA isolated from the individual's peripheral blood was subjected to polymerase chain reaction amplification and subsequent sequence analysis of a 592 base‐pair segment upstream from the CYP3A coding region. The analysis revealed no variation from wild‐type in the nucleotide present at position −290, previously suggested to influence expression and/or activity of CYP3A. The functional significance of this promoter region mutation is unclear and requires further evaluation.</description><subject>Adult</subject><subject>Alprazolam - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>General pharmacology</subject><subject>Genotype</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic Clearance Rate</subject><subject>Mixed Function Oxygenases - genetics</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Promoter Regions, Genetic</subject><subject>Trazodone - pharmacokinetics</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb2O1DAUhS0EYmcXHoAGuUBUG7j-yV85ioAFjcQIZkFUkePcMFmceNZOFM1WtHQ8I0-Co4wEEgWF7Wv5O-fax4Q8YfCCsTR9CZAzngIA5wBZKrN7ZMXimEcyAXmfrObzaAbOyLn3NwAskTF7SM4YJInMeboiP6770Y_KmCPd2IkWBpVTvUZqG7qbLC2-bMWafhwrPzg1oL-ka3Nw6s4a1VHV13Q3b2rb4yVte6roJ2vGfkB0s-gG9UCndtjTz62pf33_uTsecPGUdOtsZ4cAfsCvre0fkQeNMh4fn9YLcv361a64ijbv37wt1ptIS5aFp1WZRiUFasW1xkpoEXPAvK64AqaF5rWoARFyaLSsGpbphAWacZkqLXJxQZ4vvgdnb0f0Q9m1XqMxqkc7-jKFLMtzmEG2gNpZ7x025cG1nXLHkkE551_-k3_QPD2Zj1WH9V-KJfAAPDsBymtlmjns1v_heBx-KQ6YXLDJmhCR_2bGCV25R2WGfegLIEPfiM_VPEVhMB5kyUnWGjz-_77lu2J7lYpM_AYr1az_</recordid><startdate>200002</startdate><enddate>200002</enddate><creator>Moltke, Lisa L.</creator><creator>Tran, Thanh Huu</creator><creator>Cotreau, Monette M.</creator><creator>Greenblatt, David J.</creator><general>Blackwell Publishing Ltd</general><general>SAGE Publications</general><general>Sage Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200002</creationdate><title>Unusually Low Clearance of Two CYP3A Substrates, Alprazolam and Trazodone, in a Volunteer Subject with Wild‐Type CYP3A4 Promoter Region</title><author>Moltke, Lisa L. ; Tran, Thanh Huu ; Cotreau, Monette M. ; Greenblatt, David J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4182-4b8cea43eca2cceb3c3520e9db2a01c3c2d3d0ee090fc4bf18c613ec1247ac393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult</topic><topic>Alprazolam - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>General pharmacology</topic><topic>Genotype</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic Clearance Rate</topic><topic>Mixed Function Oxygenases - genetics</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Promoter Regions, Genetic</topic><topic>Trazodone - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moltke, Lisa L.</creatorcontrib><creatorcontrib>Tran, Thanh Huu</creatorcontrib><creatorcontrib>Cotreau, Monette M.</creatorcontrib><creatorcontrib>Greenblatt, David J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moltke, Lisa L.</au><au>Tran, Thanh Huu</au><au>Cotreau, Monette M.</au><au>Greenblatt, David J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unusually Low Clearance of Two CYP3A Substrates, Alprazolam and Trazodone, in a Volunteer Subject with Wild‐Type CYP3A4 Promoter Region</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>J Clin Pharmacol</addtitle><date>2000-02</date><risdate>2000</risdate><volume>40</volume><issue>2</issue><spage>200</spage><epage>204</epage><pages>200-204</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><coden>JCPCBR</coden><abstract>A healthy 40‐year‐old Caucasian male volunteer displayed unusually low clearance and long elimination half‐life of alprazolam and trazodone, two CYP3A substrate drugs, following single‐dose oral administration in clinical pharmacokinetic studies. Genomic DNA isolated from the individual's peripheral blood was subjected to polymerase chain reaction amplification and subsequent sequence analysis of a 592 base‐pair segment upstream from the CYP3A coding region. The analysis revealed no variation from wild‐type in the nucleotide present at position −290, previously suggested to influence expression and/or activity of CYP3A. The functional significance of this promoter region mutation is unclear and requires further evaluation.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>10664927</pmid><doi>10.1177/00912700022008748</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0091-2700 |
| ispartof | Journal of clinical pharmacology, 2000-02, Vol.40 (2), p.200-204 |
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| subjects | Adult Alprazolam - pharmacokinetics Biological and medical sciences Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - genetics General pharmacology Genotype Humans Male Medical sciences Metabolic Clearance Rate Mixed Function Oxygenases - genetics Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Promoter Regions, Genetic Trazodone - pharmacokinetics |
| title | Unusually Low Clearance of Two CYP3A Substrates, Alprazolam and Trazodone, in a Volunteer Subject with Wild‐Type CYP3A4 Promoter Region |
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