Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport
To investigate the intracellular accumulation of HIV protease inhibitors (PI) and to assess the effect of active transport on this accumulation. CEM cells were incubated with a PI for 18 h and the intracellular concentration determined using cell number and radioactivity. The effect of active transp...
Gespeichert in:
| Veröffentlicht in: | AIDS (London) 2001-04, Vol.15 (6), p.675-681 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 681 |
|---|---|
| container_issue | 6 |
| container_start_page | 675 |
| container_title | AIDS (London) |
| container_volume | 15 |
| creator | JONES, Kevin HOGGARD, Patrick G SALES, Sean D KHOO, Saye DAVEY, Ross BACK, David J |
| description | To investigate the intracellular accumulation of HIV protease inhibitors (PI) and to assess the effect of active transport on this accumulation.
CEM cells were incubated with a PI for 18 h and the intracellular concentration determined using cell number and radioactivity. The effect of active transport was investigated using cells expressing P-glycoprotein (CEM(VBL)) and cells expressing multidrug resistance-associated protein 1 (MRP1; CEM(E1000)). Incubations were also carried out at 4 degrees C and in the presence of 2-deoxyglucose plus rotenone to examine the effect of inhibiting active transport.
Nelfinavir (NFV) accumulated to the greatest extent (> 80-fold) followed by saquinavir (SQV; approximately 30-fold), ritonavir (RTV; 3-7-fold) and finally indinavir (IDV; extracellular equivalent to intracellular). In CEM(VBL) cells there was a significant reduction in the intracellular accumulation of NFV, SQV and RTV and in CEM(E1000) cells there was reduced accumulation of SQV and RTV. Inhibition of active transport processes caused a reduction in SQV and RTV accumulation but had no effect on IDV accumulation in all cell types. NFV accumulation was increased in CEM(VBL) cells as a result of inhibition of active transport.
Marked differences can be detected in the intracellular accumulation of HIV PI drugs in vitro. Both P-glycoprotein and MRP1 may play a role in limiting the intracellular concentration of the PI and active influx mechanisms may contribute to drug accumulation. |
| doi_str_mv | 10.1097/00002030-200104130-00002 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70860137</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70860137</sourcerecordid><originalsourceid>FETCH-LOGICAL-c421t-bb2c634557765226b781f0961c46ad5f58ed92f8a70de6886b71f34718d8924d3</originalsourceid><addsrcrecordid>eNqFkctOwzAQRS0EoqXwC8gLxC7gcRzbWaLyaKVKbIBt5Di2apQmxXYq8fe4Dx47vJnR6NwZz1yEMJAbIKW4JelRkpOMEgKEQcp2pSM0BibyrCgEHKMxobzMylyQEToL4T0RBZHyFI0AcgFcwhjFe2et8abTJmDX4bg0KUSvtGnboVUeK62HVcqi6zvcWzybv-G176NRYYsuXe1i73fijYu-x6prdm1MaqzjVqJ0dBuDU9curHsfz9GJVW0wF4c4Qa-PDy_TWbZ4fppP7xaZZhRiVtdU85ylZQQvKOW1kGBJyUEzrprCFtI0JbVSCdIYLmUCwOZMgGxkSVmTT9D1vm_678dgQqxWLmwXU53ph1AJIjlJp_gXBCEFZeniEyT3oPZ9CN7Yau3dSvnPCki1tab6tqb6sWZfStLLw4yhXpnmV3jwIgFXB0AFrVqbrqVd-DMglyxhX8zcljQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17872420</pqid></control><display><type>article</type><title>Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Complete</source><creator>JONES, Kevin ; HOGGARD, Patrick G ; SALES, Sean D ; KHOO, Saye ; DAVEY, Ross ; BACK, David J</creator><creatorcontrib>JONES, Kevin ; HOGGARD, Patrick G ; SALES, Sean D ; KHOO, Saye ; DAVEY, Ross ; BACK, David J</creatorcontrib><description>To investigate the intracellular accumulation of HIV protease inhibitors (PI) and to assess the effect of active transport on this accumulation.
CEM cells were incubated with a PI for 18 h and the intracellular concentration determined using cell number and radioactivity. The effect of active transport was investigated using cells expressing P-glycoprotein (CEM(VBL)) and cells expressing multidrug resistance-associated protein 1 (MRP1; CEM(E1000)). Incubations were also carried out at 4 degrees C and in the presence of 2-deoxyglucose plus rotenone to examine the effect of inhibiting active transport.
Nelfinavir (NFV) accumulated to the greatest extent (> 80-fold) followed by saquinavir (SQV; approximately 30-fold), ritonavir (RTV; 3-7-fold) and finally indinavir (IDV; extracellular equivalent to intracellular). In CEM(VBL) cells there was a significant reduction in the intracellular accumulation of NFV, SQV and RTV and in CEM(E1000) cells there was reduced accumulation of SQV and RTV. Inhibition of active transport processes caused a reduction in SQV and RTV accumulation but had no effect on IDV accumulation in all cell types. NFV accumulation was increased in CEM(VBL) cells as a result of inhibition of active transport.
Marked differences can be detected in the intracellular accumulation of HIV PI drugs in vitro. Both P-glycoprotein and MRP1 may play a role in limiting the intracellular concentration of the PI and active influx mechanisms may contribute to drug accumulation.</description><identifier>ISSN: 0269-9370</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/00002030-200104130-00002</identifier><identifier>PMID: 11371681</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>AIDS/HIV ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; ATP-Binding Cassette Transporters - metabolism ; Biological and medical sciences ; Biological Transport, Active ; Cell Line ; Glycoprotein P ; HIV Protease Inhibitors - metabolism ; Human immunodeficiency virus ; Humans ; In Vitro Techniques ; Indinavir - metabolism ; Medical sciences ; MRP1 protein ; Multidrug Resistance-Associated Proteins ; Nelfinavir - metabolism ; Pharmacology. Drug treatments ; Reverse Transcriptase Polymerase Chain Reaction ; Ritonavir - metabolism ; Saquinavir - metabolism</subject><ispartof>AIDS (London), 2001-04, Vol.15 (6), p.675-681</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-bb2c634557765226b781f0961c46ad5f58ed92f8a70de6886b71f34718d8924d3</citedby><cites>FETCH-LOGICAL-c421t-bb2c634557765226b781f0961c46ad5f58ed92f8a70de6886b71f34718d8924d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1038481$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11371681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JONES, Kevin</creatorcontrib><creatorcontrib>HOGGARD, Patrick G</creatorcontrib><creatorcontrib>SALES, Sean D</creatorcontrib><creatorcontrib>KHOO, Saye</creatorcontrib><creatorcontrib>DAVEY, Ross</creatorcontrib><creatorcontrib>BACK, David J</creatorcontrib><title>Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>To investigate the intracellular accumulation of HIV protease inhibitors (PI) and to assess the effect of active transport on this accumulation.
CEM cells were incubated with a PI for 18 h and the intracellular concentration determined using cell number and radioactivity. The effect of active transport was investigated using cells expressing P-glycoprotein (CEM(VBL)) and cells expressing multidrug resistance-associated protein 1 (MRP1; CEM(E1000)). Incubations were also carried out at 4 degrees C and in the presence of 2-deoxyglucose plus rotenone to examine the effect of inhibiting active transport.
Nelfinavir (NFV) accumulated to the greatest extent (> 80-fold) followed by saquinavir (SQV; approximately 30-fold), ritonavir (RTV; 3-7-fold) and finally indinavir (IDV; extracellular equivalent to intracellular). In CEM(VBL) cells there was a significant reduction in the intracellular accumulation of NFV, SQV and RTV and in CEM(E1000) cells there was reduced accumulation of SQV and RTV. Inhibition of active transport processes caused a reduction in SQV and RTV accumulation but had no effect on IDV accumulation in all cell types. NFV accumulation was increased in CEM(VBL) cells as a result of inhibition of active transport.
Marked differences can be detected in the intracellular accumulation of HIV PI drugs in vitro. Both P-glycoprotein and MRP1 may play a role in limiting the intracellular concentration of the PI and active influx mechanisms may contribute to drug accumulation.</description><subject>AIDS/HIV</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biological Transport, Active</subject><subject>Cell Line</subject><subject>Glycoprotein P</subject><subject>HIV Protease Inhibitors - metabolism</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Indinavir - metabolism</subject><subject>Medical sciences</subject><subject>MRP1 protein</subject><subject>Multidrug Resistance-Associated Proteins</subject><subject>Nelfinavir - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Ritonavir - metabolism</subject><subject>Saquinavir - metabolism</subject><issn>0269-9370</issn><issn>1473-5571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctOwzAQRS0EoqXwC8gLxC7gcRzbWaLyaKVKbIBt5Di2apQmxXYq8fe4Dx47vJnR6NwZz1yEMJAbIKW4JelRkpOMEgKEQcp2pSM0BibyrCgEHKMxobzMylyQEToL4T0RBZHyFI0AcgFcwhjFe2et8abTJmDX4bg0KUSvtGnboVUeK62HVcqi6zvcWzybv-G176NRYYsuXe1i73fijYu-x6prdm1MaqzjVqJ0dBuDU9curHsfz9GJVW0wF4c4Qa-PDy_TWbZ4fppP7xaZZhRiVtdU85ylZQQvKOW1kGBJyUEzrprCFtI0JbVSCdIYLmUCwOZMgGxkSVmTT9D1vm_678dgQqxWLmwXU53ph1AJIjlJp_gXBCEFZeniEyT3oPZ9CN7Yau3dSvnPCki1tab6tqb6sWZfStLLw4yhXpnmV3jwIgFXB0AFrVqbrqVd-DMglyxhX8zcljQ</recordid><startdate>20010413</startdate><enddate>20010413</enddate><creator>JONES, Kevin</creator><creator>HOGGARD, Patrick G</creator><creator>SALES, Sean D</creator><creator>KHOO, Saye</creator><creator>DAVEY, Ross</creator><creator>BACK, David J</creator><general>Lippincott Williams & Wilkins</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>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20010413</creationdate><title>Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport</title><author>JONES, Kevin ; HOGGARD, Patrick G ; SALES, Sean D ; KHOO, Saye ; DAVEY, Ross ; BACK, David J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-bb2c634557765226b781f0961c46ad5f58ed92f8a70de6886b71f34718d8924d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>AIDS/HIV</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biological Transport, Active</topic><topic>Cell Line</topic><topic>Glycoprotein P</topic><topic>HIV Protease Inhibitors - metabolism</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Indinavir - metabolism</topic><topic>Medical sciences</topic><topic>MRP1 protein</topic><topic>Multidrug Resistance-Associated Proteins</topic><topic>Nelfinavir - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Ritonavir - metabolism</topic><topic>Saquinavir - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JONES, Kevin</creatorcontrib><creatorcontrib>HOGGARD, Patrick G</creatorcontrib><creatorcontrib>SALES, Sean D</creatorcontrib><creatorcontrib>KHOO, Saye</creatorcontrib><creatorcontrib>DAVEY, Ross</creatorcontrib><creatorcontrib>BACK, 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>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>AIDS (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JONES, Kevin</au><au>HOGGARD, Patrick G</au><au>SALES, Sean D</au><au>KHOO, Saye</au><au>DAVEY, Ross</au><au>BACK, David J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport</atitle><jtitle>AIDS (London)</jtitle><addtitle>AIDS</addtitle><date>2001-04-13</date><risdate>2001</risdate><volume>15</volume><issue>6</issue><spage>675</spage><epage>681</epage><pages>675-681</pages><issn>0269-9370</issn><eissn>1473-5571</eissn><abstract>To investigate the intracellular accumulation of HIV protease inhibitors (PI) and to assess the effect of active transport on this accumulation.
CEM cells were incubated with a PI for 18 h and the intracellular concentration determined using cell number and radioactivity. The effect of active transport was investigated using cells expressing P-glycoprotein (CEM(VBL)) and cells expressing multidrug resistance-associated protein 1 (MRP1; CEM(E1000)). Incubations were also carried out at 4 degrees C and in the presence of 2-deoxyglucose plus rotenone to examine the effect of inhibiting active transport.
Nelfinavir (NFV) accumulated to the greatest extent (> 80-fold) followed by saquinavir (SQV; approximately 30-fold), ritonavir (RTV; 3-7-fold) and finally indinavir (IDV; extracellular equivalent to intracellular). In CEM(VBL) cells there was a significant reduction in the intracellular accumulation of NFV, SQV and RTV and in CEM(E1000) cells there was reduced accumulation of SQV and RTV. Inhibition of active transport processes caused a reduction in SQV and RTV accumulation but had no effect on IDV accumulation in all cell types. NFV accumulation was increased in CEM(VBL) cells as a result of inhibition of active transport.
Marked differences can be detected in the intracellular accumulation of HIV PI drugs in vitro. Both P-glycoprotein and MRP1 may play a role in limiting the intracellular concentration of the PI and active influx mechanisms may contribute to drug accumulation.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>11371681</pmid><doi>10.1097/00002030-200104130-00002</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0269-9370 |
| ispartof | AIDS (London), 2001-04, Vol.15 (6), p.675-681 |
| issn | 0269-9370 1473-5571 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70860137 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | AIDS/HIV Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ATP-Binding Cassette Transporters - metabolism Biological and medical sciences Biological Transport, Active Cell Line Glycoprotein P HIV Protease Inhibitors - metabolism Human immunodeficiency virus Humans In Vitro Techniques Indinavir - metabolism Medical sciences MRP1 protein Multidrug Resistance-Associated Proteins Nelfinavir - metabolism Pharmacology. Drug treatments Reverse Transcriptase Polymerase Chain Reaction Ritonavir - metabolism Saquinavir - metabolism |
| title | Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T23%3A06%3A58IST&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=Differences%20in%20the%20intracellular%20accumulation%20of%20HIV%20protease%20inhibitors%20in%20vitro%20and%20the%20effect%20of%20active%20transport&rft.jtitle=AIDS%20(London)&rft.au=JONES,%20Kevin&rft.date=2001-04-13&rft.volume=15&rft.issue=6&rft.spage=675&rft.epage=681&rft.pages=675-681&rft.issn=0269-9370&rft.eissn=1473-5571&rft_id=info:doi/10.1097/00002030-200104130-00002&rft_dat=%3Cproquest_cross%3E70860137%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17872420&rft_id=info:pmid/11371681&rfr_iscdi=true |