Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans

Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter‐mediated drug–drug inter...

Full description

Saved in:
Bibliographic Details
Published in:Journal of clinical pharmacology 2016-07, Vol.56 (S7), p.S82-S98
Main Authors: Momper, Jeremiah D., Tsunoda, Shirley M., Ma, Joseph D.
Format: Article
Language:English
Subjects:
Animals
ATP-Binding Cassette Transporters
Biological Transport - drug effects
Biological Transport - physiology
biomarker
Decision Trees
drug development
Drug Evaluation, Preclinical - methods
Drug Interactions - physiology
drug-drug interaction
Humans
Membrane Transport Modulators - metabolism
Membrane Transport Modulators - pharmacology
Membrane Transport Proteins - metabolism
Organic Anion Transporters - metabolism
Organic Cation Transport Proteins - metabolism
Pharmaceutical Preparations - administration & dosage
Pharmaceutical Preparations - metabolism
Phenotype
phenotyping
Substrate Specificity - physiology
transporter
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c5327-e6009a5ebf166a913b12b7f4d226c367246c2969d702aaaba06346870e754fb73
cites cdi_FETCH-LOGICAL-c5327-e6009a5ebf166a913b12b7f4d226c367246c2969d702aaaba06346870e754fb73
container_end_page S98
container_issue S7
container_start_page S82
container_title Journal of clinical pharmacology
container_volume 56
creator Momper, Jeremiah D.
Tsunoda, Shirley M.
Ma, Joseph D.
description Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter‐mediated drug–drug interactions. The transporters are P‐glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter‐mediated drug–drug interaction study is needed. Phenotyping is a methodology that evaluates real‐time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter.
doi_str_mv 10.1002/jcph.736
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1803790018</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4109854071</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5327-e6009a5ebf166a913b12b7f4d226c367246c2969d702aaaba06346870e754fb73</originalsourceid><addsrcrecordid>eNp1kV9v2yAUxdG0qc3aSvsEE9Je9uKOPzbYj1XUNa2iLVK75RGBg2dSG1zA6fLth5WskyaVF9C9Pw6HewD4gNElRoh82dZDe8kpewNmuChIljOUvwUzhCqcEY7QKXgfwhYhzPICn4BTwmlZ4JLMQH-9k90oo3EWugauvBtc0Bt4a-FPs3NTQWl4P6oQvYw6QGmnZmuUic4H2DgPV622Lu4HY3_BBy9tGJyP2sOrOpqdiXtoLFyMfWqcg3eN7IK-OO5n4MfX64f5Ilt-v7mdXy2zuqCEZ5ol57LQqsGMyQpThYniTb4hhNWUcZKzmlSs2nBEpJRKIkZzVnKkeZE3itMz8PmgO3j3NOoQRW9CrbtOWu3GIHCJKK_SPMqEfvoP3brR2-RuogiuMKfon2DtXQheN2Lwppd-LzASUwRiikCkCBL68Sg4ql5vXsC_M09AfgCeXZfGFB678Vl70WrZxVagtPIUWUZSWigdeDaVpj9lx2um0_tX3xd389Xi4OPImxD17xde-kfBOOWFWH-7Eetqcbde3mNR0D_iBq5n</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1802191730</pqid></control><display><type>article</type><title>Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans</title><source>Wiley</source><creator>Momper, Jeremiah D. ; Tsunoda, Shirley M. ; Ma, Joseph D.</creator><creatorcontrib>Momper, Jeremiah D. ; Tsunoda, Shirley M. ; Ma, Joseph D.</creatorcontrib><description>Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter‐mediated drug–drug interactions. The transporters are P‐glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter‐mediated drug–drug interaction study is needed. Phenotyping is a methodology that evaluates real‐time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1002/jcph.736</identifier><identifier>PMID: 27385182</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Animals ; ATP-Binding Cassette Transporters ; Biological Transport - drug effects ; Biological Transport - physiology ; biomarker ; Decision Trees ; drug development ; Drug Evaluation, Preclinical - methods ; Drug Interactions - physiology ; drug-drug interaction ; Humans ; Membrane Transport Modulators - metabolism ; Membrane Transport Modulators - pharmacology ; Membrane Transport Proteins - metabolism ; Organic Anion Transporters - metabolism ; Organic Cation Transport Proteins - metabolism ; Pharmaceutical Preparations - administration &amp; dosage ; Pharmaceutical Preparations - metabolism ; Phenotype ; phenotyping ; Substrate Specificity - physiology ; transporter</subject><ispartof>Journal of clinical pharmacology, 2016-07, Vol.56 (S7), p.S82-S98</ispartof><rights>2016, The American College of Clinical Pharmacology</rights><rights>2016 American College of Clinical Pharmacology</rights><rights>2016, The American College of Clinical Pharmacology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5327-e6009a5ebf166a913b12b7f4d226c367246c2969d702aaaba06346870e754fb73</citedby><cites>FETCH-LOGICAL-c5327-e6009a5ebf166a913b12b7f4d226c367246c2969d702aaaba06346870e754fb73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcph.736$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcph.736$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27385182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Momper, Jeremiah D.</creatorcontrib><creatorcontrib>Tsunoda, Shirley M.</creatorcontrib><creatorcontrib>Ma, Joseph D.</creatorcontrib><title>Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans</title><title>Journal of clinical pharmacology</title><addtitle>The Journal of Clinical Pharmacology</addtitle><description>Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter‐mediated drug–drug interactions. The transporters are P‐glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter‐mediated drug–drug interaction study is needed. Phenotyping is a methodology that evaluates real‐time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter.</description><subject>Animals</subject><subject>ATP-Binding Cassette Transporters</subject><subject>Biological Transport - drug effects</subject><subject>Biological Transport - physiology</subject><subject>biomarker</subject><subject>Decision Trees</subject><subject>drug development</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Drug Interactions - physiology</subject><subject>drug-drug interaction</subject><subject>Humans</subject><subject>Membrane Transport Modulators - metabolism</subject><subject>Membrane Transport Modulators - pharmacology</subject><subject>Membrane Transport Proteins - metabolism</subject><subject>Organic Anion Transporters - metabolism</subject><subject>Organic Cation Transport Proteins - metabolism</subject><subject>Pharmaceutical Preparations - administration &amp; dosage</subject><subject>Pharmaceutical Preparations - metabolism</subject><subject>Phenotype</subject><subject>phenotyping</subject><subject>Substrate Specificity - physiology</subject><subject>transporter</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp1kV9v2yAUxdG0qc3aSvsEE9Je9uKOPzbYj1XUNa2iLVK75RGBg2dSG1zA6fLth5WskyaVF9C9Pw6HewD4gNElRoh82dZDe8kpewNmuChIljOUvwUzhCqcEY7QKXgfwhYhzPICn4BTwmlZ4JLMQH-9k90oo3EWugauvBtc0Bt4a-FPs3NTQWl4P6oQvYw6QGmnZmuUic4H2DgPV622Lu4HY3_BBy9tGJyP2sOrOpqdiXtoLFyMfWqcg3eN7IK-OO5n4MfX64f5Ilt-v7mdXy2zuqCEZ5ol57LQqsGMyQpThYniTb4hhNWUcZKzmlSs2nBEpJRKIkZzVnKkeZE3itMz8PmgO3j3NOoQRW9CrbtOWu3GIHCJKK_SPMqEfvoP3brR2-RuogiuMKfon2DtXQheN2Lwppd-LzASUwRiikCkCBL68Sg4ql5vXsC_M09AfgCeXZfGFB678Vl70WrZxVagtPIUWUZSWigdeDaVpj9lx2um0_tX3xd389Xi4OPImxD17xde-kfBOOWFWH-7Eetqcbde3mNR0D_iBq5n</recordid><startdate>201607</startdate><enddate>201607</enddate><creator>Momper, Jeremiah D.</creator><creator>Tsunoda, Shirley M.</creator><creator>Ma, Joseph D.</creator><general>Blackwell Publishing Ltd</general><general>American College of Clinical Pharmacology</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201607</creationdate><title>Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans</title><author>Momper, Jeremiah D. ; Tsunoda, Shirley M. ; Ma, Joseph D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5327-e6009a5ebf166a913b12b7f4d226c367246c2969d702aaaba06346870e754fb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>ATP-Binding Cassette Transporters</topic><topic>Biological Transport - drug effects</topic><topic>Biological Transport - physiology</topic><topic>biomarker</topic><topic>Decision Trees</topic><topic>drug development</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Drug Interactions - physiology</topic><topic>drug-drug interaction</topic><topic>Humans</topic><topic>Membrane Transport Modulators - metabolism</topic><topic>Membrane Transport Modulators - pharmacology</topic><topic>Membrane Transport Proteins - metabolism</topic><topic>Organic Anion Transporters - metabolism</topic><topic>Organic Cation Transport Proteins - metabolism</topic><topic>Pharmaceutical Preparations - administration &amp; dosage</topic><topic>Pharmaceutical Preparations - metabolism</topic><topic>Phenotype</topic><topic>phenotyping</topic><topic>Substrate Specificity - physiology</topic><topic>transporter</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Momper, Jeremiah D.</creatorcontrib><creatorcontrib>Tsunoda, Shirley M.</creatorcontrib><creatorcontrib>Ma, Joseph D.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Momper, Jeremiah D.</au><au>Tsunoda, Shirley M.</au><au>Ma, Joseph D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>The Journal of Clinical Pharmacology</addtitle><date>2016-07</date><risdate>2016</risdate><volume>56</volume><issue>S7</issue><spage>S82</spage><epage>S98</epage><pages>S82-S98</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><notes>ark:/67375/WNG-W9HJWLS1-5</notes><notes>istex:32BC1F9246115D573BF70C801225A26AD4BBEAD9</notes><notes>ArticleID:JCPH736</notes><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-3</notes><notes>content type line 23</notes><notes>ObjectType-Review-1</notes><abstract>Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter‐mediated drug–drug interactions. The transporters are P‐glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter‐mediated drug–drug interaction study is needed. Phenotyping is a methodology that evaluates real‐time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>27385182</pmid><doi>10.1002/jcph.736</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0091-2700
ispartof Journal of clinical pharmacology, 2016-07, Vol.56 (S7), p.S82-S98
issn 0091-2700
1552-4604
language eng
recordid cdi_proquest_miscellaneous_1803790018
source Wiley
subjects Animals
ATP-Binding Cassette Transporters
Biological Transport - drug effects
Biological Transport - physiology
biomarker
Decision Trees
drug development
Drug Evaluation, Preclinical - methods
Drug Interactions - physiology
drug-drug interaction
Humans
Membrane Transport Modulators - metabolism
Membrane Transport Modulators - pharmacology
Membrane Transport Proteins - metabolism
Organic Anion Transporters - metabolism
Organic Cation Transport Proteins - metabolism
Pharmaceutical Preparations - administration & dosage
Pharmaceutical Preparations - metabolism
Phenotype
phenotyping
Substrate Specificity - physiology
transporter
title Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T17%3A26%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20Proposed%20In%20Vivo%20Probe%20Substrates%20and%20Inhibitors%20for%20Phenotyping%20Transporter%20Activity%20in%20Humans&rft.jtitle=Journal%20of%20clinical%20pharmacology&rft.au=Momper,%20Jeremiah%20D.&rft.date=2016-07&rft.volume=56&rft.issue=S7&rft.spage=S82&rft.epage=S98&rft.pages=S82-S98&rft.issn=0091-2700&rft.eissn=1552-4604&rft_id=info:doi/10.1002/jcph.736&rft_dat=%3Cproquest_cross%3E4109854071%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c5327-e6009a5ebf166a913b12b7f4d226c367246c2969d702aaaba06346870e754fb73%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1802191730&rft_id=info:pmid/27385182&rfr_iscdi=true