Quantitative Imaging and Sigmoidoscopy to Assess Distribution of Rectal Microbicide Surrogates
Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose‐based microbicide surrogate or viscosity‐matched semen surrogate, labeled with gadolinium‐DTPA (diethy...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2008-01, Vol.83 (1), p.97-105 |
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| creator | Hendrix, C W Fuchs, E J Macura, K J Lee, L A Parsons, T L Bakshi, R P Khan, W A Guidos, A Leal, J P Wahl, R |
| description | Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose‐based microbicide surrogate or viscosity‐matched semen surrogate, labeled with gadolinium‐DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium‐sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29–102%; P |
| doi_str_mv | 10.1038/sj.clpt.6100236 |
| format | Article |
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Clinical Pharmacology & Therapeutics (2008) 83, 97–105; doi:10.1038/sj.clpt.6100236; published online 16 May 2007</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1038/sj.clpt.6100236</identifier><identifier>PMID: 17507921</identifier><identifier>CODEN: CLPTAT</identifier><language>eng</language><publisher>New York, NY: Nature Publishing</publisher><subject><![CDATA[Administration, Rectal ; Adult ; Anti-HIV Agents - administration & dosage ; Anti-HIV Agents - metabolism ; Anti-HIV Agents - therapeutic use ; Anti-Infective Agents, Local - administration & dosage ; Anti-Infective Agents, Local - metabolism ; Anti-Infective Agents, Local - therapeutic use ; Biological and medical sciences ; Cellulose - administration & dosage ; Cellulose - analogs & derivatives ; Cellulose - metabolism ; Cellulose - therapeutic use ; Coitus ; Contrast Media ; Diagnostic Imaging - methods ; Ejaculation ; Enema ; Feasibility Studies ; Gadolinium DTPA - administration & dosage ; Gels ; HIV Infections - metabolism ; HIV Infections - pathology ; HIV Infections - prevention & control ; Humans ; Magnetic Resonance Imaging ; Medical sciences ; Pharmacology. Drug treatments ; Pilot Projects ; Radiopharmaceuticals - administration & dosage ; Rectum - metabolism ; Rectum - pathology ; Semen - metabolism ; Sigmoidoscopy ; Technetium Tc 99m Sulfur Colloid - administration & dosage ; Time Factors ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed ; Unsafe Sex]]></subject><ispartof>Clinical pharmacology and therapeutics, 2008-01, Vol.83 (1), p.97-105</ispartof><rights>2008 American Society for Clinical Pharmacology and Therapeutics</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3736-e716b51dfe55f22e91ed0ea13ce5f5fa2619e17dbef171d15534475efb07607b3</citedby><cites>FETCH-LOGICAL-c3736-e716b51dfe55f22e91ed0ea13ce5f5fa2619e17dbef171d15534475efb07607b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Fsj.clpt.6100236$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Fsj.clpt.6100236$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20016995$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17507921$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hendrix, C W</creatorcontrib><creatorcontrib>Fuchs, E J</creatorcontrib><creatorcontrib>Macura, K J</creatorcontrib><creatorcontrib>Lee, L A</creatorcontrib><creatorcontrib>Parsons, T L</creatorcontrib><creatorcontrib>Bakshi, R P</creatorcontrib><creatorcontrib>Khan, W A</creatorcontrib><creatorcontrib>Guidos, A</creatorcontrib><creatorcontrib>Leal, J P</creatorcontrib><creatorcontrib>Wahl, R</creatorcontrib><title>Quantitative Imaging and Sigmoidoscopy to Assess Distribution of Rectal Microbicide Surrogates</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose‐based microbicide surrogate or viscosity‐matched semen surrogate, labeled with gadolinium‐DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium‐sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29–102%; P<0.001), as far as the splenic flexure (~60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV‐sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.
Clinical Pharmacology & Therapeutics (2008) 83, 97–105; doi:10.1038/sj.clpt.6100236; published online 16 May 2007</description><subject>Administration, Rectal</subject><subject>Adult</subject><subject>Anti-HIV Agents - administration & dosage</subject><subject>Anti-HIV Agents - metabolism</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Anti-Infective Agents, Local - administration & dosage</subject><subject>Anti-Infective Agents, Local - metabolism</subject><subject>Anti-Infective Agents, Local - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cellulose - administration & dosage</subject><subject>Cellulose - analogs & derivatives</subject><subject>Cellulose - metabolism</subject><subject>Cellulose - therapeutic use</subject><subject>Coitus</subject><subject>Contrast Media</subject><subject>Diagnostic Imaging - methods</subject><subject>Ejaculation</subject><subject>Enema</subject><subject>Feasibility Studies</subject><subject>Gadolinium DTPA - administration & dosage</subject><subject>Gels</subject><subject>HIV Infections - metabolism</subject><subject>HIV Infections - pathology</subject><subject>HIV Infections - prevention & control</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Pilot Projects</subject><subject>Radiopharmaceuticals - administration & dosage</subject><subject>Rectum - metabolism</subject><subject>Rectum - pathology</subject><subject>Semen - metabolism</subject><subject>Sigmoidoscopy</subject><subject>Technetium Tc 99m Sulfur Colloid - administration & dosage</subject><subject>Time Factors</subject><subject>Tissue Distribution</subject><subject>Tomography, Emission-Computed, Single-Photon</subject><subject>Tomography, X-Ray Computed</subject><subject>Unsafe Sex</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1vEzEQhi0EoiFw5oZ8obdN7XW8jo9VWkqlIugHVyyvdxw52l0Hj5cq_74bZWmPPY1m9My8o4eQz5wtOBOrM9wuXLvLi4ozVorqDZlxKcqikkK-JTPGmC70OD8hHxC3Y7vUq9V7csKVZEqXfEb-3A62zyHbHP4Bve7sJvQbavuG3odNF0MT0cXdnuZIzxEBkV4EzCnUQw6xp9HTO3DZtvRHcCnWwYUG6P2QUtzYDPiRvPO2Rfg01Tn5_e3yYf29uPl5db0-vymcUKIqQPGqlrzxIKUvS9AcGgaWCwfSS2_LimvgqqnBc8UbLqVYLpUEXzNVMVWLOTk93t2l-HcAzKYL6KBtbQ9xQKMYr6Qe3czJ2REcv0VM4M0uhc6mveHMHJQa3JqDUjMpHTe-TKeHuoPmhZ8cjsDXCbDobOuT7V3AZ65kY7bWh2h15B5DC_vXcs3618P_F54AXhqS0w</recordid><startdate>200801</startdate><enddate>200801</enddate><creator>Hendrix, C W</creator><creator>Fuchs, E J</creator><creator>Macura, K J</creator><creator>Lee, L A</creator><creator>Parsons, T L</creator><creator>Bakshi, R P</creator><creator>Khan, W A</creator><creator>Guidos, A</creator><creator>Leal, J P</creator><creator>Wahl, R</creator><general>Nature Publishing</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>200801</creationdate><title>Quantitative Imaging and Sigmoidoscopy to Assess Distribution of Rectal Microbicide Surrogates</title><author>Hendrix, C W ; Fuchs, E J ; Macura, K J ; Lee, L A ; Parsons, T L ; Bakshi, R P ; Khan, W A ; Guidos, A ; Leal, J P ; Wahl, R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3736-e716b51dfe55f22e91ed0ea13ce5f5fa2619e17dbef171d15534475efb07607b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Administration, Rectal</topic><topic>Adult</topic><topic>Anti-HIV Agents - administration & dosage</topic><topic>Anti-HIV Agents - metabolism</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Anti-Infective Agents, Local - administration & dosage</topic><topic>Anti-Infective Agents, Local - metabolism</topic><topic>Anti-Infective Agents, Local - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cellulose - administration & dosage</topic><topic>Cellulose - analogs & derivatives</topic><topic>Cellulose - metabolism</topic><topic>Cellulose - therapeutic use</topic><topic>Coitus</topic><topic>Contrast Media</topic><topic>Diagnostic Imaging - methods</topic><topic>Ejaculation</topic><topic>Enema</topic><topic>Feasibility Studies</topic><topic>Gadolinium DTPA - administration & dosage</topic><topic>Gels</topic><topic>HIV Infections - metabolism</topic><topic>HIV Infections - pathology</topic><topic>HIV Infections - prevention & control</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Pilot Projects</topic><topic>Radiopharmaceuticals - administration & dosage</topic><topic>Rectum - metabolism</topic><topic>Rectum - pathology</topic><topic>Semen - metabolism</topic><topic>Sigmoidoscopy</topic><topic>Technetium Tc 99m Sulfur Colloid - administration & dosage</topic><topic>Time Factors</topic><topic>Tissue Distribution</topic><topic>Tomography, Emission-Computed, Single-Photon</topic><topic>Tomography, X-Ray Computed</topic><topic>Unsafe Sex</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hendrix, C W</creatorcontrib><creatorcontrib>Fuchs, E J</creatorcontrib><creatorcontrib>Macura, K J</creatorcontrib><creatorcontrib>Lee, L A</creatorcontrib><creatorcontrib>Parsons, T L</creatorcontrib><creatorcontrib>Bakshi, R P</creatorcontrib><creatorcontrib>Khan, W A</creatorcontrib><creatorcontrib>Guidos, A</creatorcontrib><creatorcontrib>Leal, J P</creatorcontrib><creatorcontrib>Wahl, R</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>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hendrix, C W</au><au>Fuchs, E J</au><au>Macura, K J</au><au>Lee, L A</au><au>Parsons, T L</au><au>Bakshi, R P</au><au>Khan, W A</au><au>Guidos, A</au><au>Leal, J P</au><au>Wahl, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantitative Imaging and Sigmoidoscopy to Assess Distribution of Rectal Microbicide Surrogates</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2008-01</date><risdate>2008</risdate><volume>83</volume><issue>1</issue><spage>97</spage><epage>105</epage><pages>97-105</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><coden>CLPTAT</coden><abstract>Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose‐based microbicide surrogate or viscosity‐matched semen surrogate, labeled with gadolinium‐DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium‐sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29–102%; P<0.001), as far as the splenic flexure (~60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV‐sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.
Clinical Pharmacology & Therapeutics (2008) 83, 97–105; doi:10.1038/sj.clpt.6100236; published online 16 May 2007</abstract><cop>New York, NY</cop><pub>Nature Publishing</pub><pmid>17507921</pmid><doi>10.1038/sj.clpt.6100236</doi><tpages>9</tpages></addata></record> |
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| subjects | Administration, Rectal Adult Anti-HIV Agents - administration & dosage Anti-HIV Agents - metabolism Anti-HIV Agents - therapeutic use Anti-Infective Agents, Local - administration & dosage Anti-Infective Agents, Local - metabolism Anti-Infective Agents, Local - therapeutic use Biological and medical sciences Cellulose - administration & dosage Cellulose - analogs & derivatives Cellulose - metabolism Cellulose - therapeutic use Coitus Contrast Media Diagnostic Imaging - methods Ejaculation Enema Feasibility Studies Gadolinium DTPA - administration & dosage Gels HIV Infections - metabolism HIV Infections - pathology HIV Infections - prevention & control Humans Magnetic Resonance Imaging Medical sciences Pharmacology. Drug treatments Pilot Projects Radiopharmaceuticals - administration & dosage Rectum - metabolism Rectum - pathology Semen - metabolism Sigmoidoscopy Technetium Tc 99m Sulfur Colloid - administration & dosage Time Factors Tissue Distribution Tomography, Emission-Computed, Single-Photon Tomography, X-Ray Computed Unsafe Sex |
| title | Quantitative Imaging and Sigmoidoscopy to Assess Distribution of Rectal Microbicide Surrogates |
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