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Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a-NGR with rh-IFNα2a administered intravenously in mice and rats
Objectives rh‐IFNα2a‐NGR is a promising anti‐tumor candidate. The aim of present study was to compare pharmacokinetics of rh‐IFNα2a‐NGR with rh‐IFNα2a. Methods Pharmacokinetics and elimination were investigated after intravenous administration to mice and rats. Compared tumor and tissue distribution...
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| Published in: | Journal of pharmacy and pharmacology 2013-04, Vol.65 (4), p.574-581 |
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| Main Authors: | , , , , , , |
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| container_end_page | 581 |
| container_issue | 4 |
| container_start_page | 574 |
| container_title | Journal of pharmacy and pharmacology |
| container_volume | 65 |
| creator | Wang, Xue-Xi Lu, Li Song, Chun-Li Qian, Wei-Na Zhang, Sheng-Yan Zhang, Ying-Qi Wu, Yong-Jie |
| description | Objectives
rh‐IFNα2a‐NGR is a promising anti‐tumor candidate. The aim of present study was to compare pharmacokinetics of rh‐IFNα2a‐NGR with rh‐IFNα2a.
Methods
Pharmacokinetics and elimination were investigated after intravenous administration to mice and rats. Compared tumor and tissue distribution profiles between rh‐IFNα2a‐NGR and rh‐IFNα2a were illustrated in the tumor transplanted mice of SP2/0 myeloma. Double antibody sandwich ELISA method was used to assess the level of both rh‐IFNα2a‐NGR and rh‐IFNα2a in serum, tissue, bile and urine.
Key findings
After a single intravenous administration, the pharmacokinetic characters of rh‐IFNα2a‐NGR and rh‐IFNα2a were described using a two‐compartment model. No significant differences were observed between the two drugs in pharmacokinetic and elimination data. However, the concentration of rh‐IFNα2a‐NGR in tumor was 5.34 times and 1.52 times as high as that of rh‐IFNα2a at 0.5 h (P |
| doi_str_mv | 10.1111/jphp.12022 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1317836789</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1317836789</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3182-64b9cce4e971eeffde2899cf68706745042b19fc6cc027a90e833adc25cc667b3</originalsourceid><addsrcrecordid>eNp9kU1OHDEQha0oKEwgmxwg8jKK1MQ_3bZ7GY0yAwgNEIGytDzuatrQf9huyJwiZ8lFcqZ4MoCyijclP331VHoPofeUHNH0Pt-OzXhEGWHsFZoxkrNM0kK9RjOSpIwXku-jtyHcEkKkEOIN2mc8V0oqOUM_50M3Gm-iewA8NsZ3xg53rofobMBDjQ2OUzdMPovG3yS1v8GxAW_GDbamr1xlImDfZCeL1e9fzGSr5Tf86GLzj4ZN1bnehQgeKuz66M0D9MMU2k364c5ZwMkKpyvCIdqrTRvg3dM8QNeLr1fz4-zsfHky_3KWWU4Vy0S-Lq2FHEpJAeq6AqbK0tZCSSJkXqQQ1rSsrbCWMGlKAopzU1lWWCuEXPMD9HHnO_rhfoIQdeeChbY1PaTLNOVUKi6kKhP6aYdaP4Tgodajd53xG02J3hagtwXovwUk-MOT77TuoHpBnxNPAN0Bj66FzX-s9OnF8cWzabbb2Wb442XH-DstJJeF_r5a6sXpUl1eXnFN-B-iK6Nu</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1317836789</pqid></control><display><type>article</type><title>Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a-NGR with rh-IFNα2a administered intravenously in mice and rats</title><source>Oxford Journals Online</source><creator>Wang, Xue-Xi ; Lu, Li ; Song, Chun-Li ; Qian, Wei-Na ; Zhang, Sheng-Yan ; Zhang, Ying-Qi ; Wu, Yong-Jie</creator><creatorcontrib>Wang, Xue-Xi ; Lu, Li ; Song, Chun-Li ; Qian, Wei-Na ; Zhang, Sheng-Yan ; Zhang, Ying-Qi ; Wu, Yong-Jie</creatorcontrib><description>Objectives
rh‐IFNα2a‐NGR is a promising anti‐tumor candidate. The aim of present study was to compare pharmacokinetics of rh‐IFNα2a‐NGR with rh‐IFNα2a.
Methods
Pharmacokinetics and elimination were investigated after intravenous administration to mice and rats. Compared tumor and tissue distribution profiles between rh‐IFNα2a‐NGR and rh‐IFNα2a were illustrated in the tumor transplanted mice of SP2/0 myeloma. Double antibody sandwich ELISA method was used to assess the level of both rh‐IFNα2a‐NGR and rh‐IFNα2a in serum, tissue, bile and urine.
Key findings
After a single intravenous administration, the pharmacokinetic characters of rh‐IFNα2a‐NGR and rh‐IFNα2a were described using a two‐compartment model. No significant differences were observed between the two drugs in pharmacokinetic and elimination data. However, the concentration of rh‐IFNα2a‐NGR in tumor was 5.34 times and 1.52 times as high as that of rh‐IFNα2a at 0.5 h (P < 0.01) and 1 h. In addition, immunohistochemical stain displayed rh‐IFNα2a‐NGR was predominantly located in tumor vascular tissues.
Conclusions
rh‐IFNα2a‐NGR could be an agent for tumor vascular‐targeting therapy and these findings provided references for further clinical study.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1111/jphp.12022</identifier><identifier>PMID: 23488787</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject><![CDATA[Angiogenesis Inhibitors - administration & dosage ; Angiogenesis Inhibitors - blood ; Angiogenesis Inhibitors - pharmacokinetics ; Angiogenesis Inhibitors - urine ; Animals ; Bile - metabolism ; Drug Delivery Systems ; Drugs, Investigational - administration & dosage ; Drugs, Investigational - metabolism ; Drugs, Investigational - pharmacokinetics ; Humans ; Injections, Intravenous ; Interferon-alpha - administration & dosage ; Interferon-alpha - genetics ; Interferon-alpha - metabolism ; Interferon-alpha - pharmacokinetics ; Mice ; Mice, Inbred Strains ; Models, Biological ; Neoplasm Transplantation ; NGR ; Oligopeptides - administration & dosage ; Oligopeptides - chemistry ; Oligopeptides - genetics ; Oligopeptides - metabolism ; pharmacokinetic ; Plasmacytoma - blood supply ; Plasmacytoma - metabolism ; Plasmacytoma - pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins - administration & dosage ; Recombinant Fusion Proteins - blood ; Recombinant Fusion Proteins - pharmacokinetics ; Recombinant Fusion Proteins - urine ; Recombinant Proteins - administration & dosage ; Recombinant Proteins - blood ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Recombinant Proteins - pharmacokinetics ; Recombinant Proteins - urine ; rh-IFNα2a ; targeted therapy ; Tissue Distribution ; tumour]]></subject><ispartof>Journal of pharmacy and pharmacology, 2013-04, Vol.65 (4), p.574-581</ispartof><rights>2013 The Authors. JPP © 2013. Royal Pharmaceutical Society</rights><rights>2013 The Authors. JPP © 2013. Royal Pharmaceutical Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3182-64b9cce4e971eeffde2899cf68706745042b19fc6cc027a90e833adc25cc667b3</citedby><cites>FETCH-LOGICAL-c3182-64b9cce4e971eeffde2899cf68706745042b19fc6cc027a90e833adc25cc667b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23488787$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xue-Xi</creatorcontrib><creatorcontrib>Lu, Li</creatorcontrib><creatorcontrib>Song, Chun-Li</creatorcontrib><creatorcontrib>Qian, Wei-Na</creatorcontrib><creatorcontrib>Zhang, Sheng-Yan</creatorcontrib><creatorcontrib>Zhang, Ying-Qi</creatorcontrib><creatorcontrib>Wu, Yong-Jie</creatorcontrib><title>Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a-NGR with rh-IFNα2a administered intravenously in mice and rats</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>Objectives
rh‐IFNα2a‐NGR is a promising anti‐tumor candidate. The aim of present study was to compare pharmacokinetics of rh‐IFNα2a‐NGR with rh‐IFNα2a.
Methods
Pharmacokinetics and elimination were investigated after intravenous administration to mice and rats. Compared tumor and tissue distribution profiles between rh‐IFNα2a‐NGR and rh‐IFNα2a were illustrated in the tumor transplanted mice of SP2/0 myeloma. Double antibody sandwich ELISA method was used to assess the level of both rh‐IFNα2a‐NGR and rh‐IFNα2a in serum, tissue, bile and urine.
Key findings
After a single intravenous administration, the pharmacokinetic characters of rh‐IFNα2a‐NGR and rh‐IFNα2a were described using a two‐compartment model. No significant differences were observed between the two drugs in pharmacokinetic and elimination data. However, the concentration of rh‐IFNα2a‐NGR in tumor was 5.34 times and 1.52 times as high as that of rh‐IFNα2a at 0.5 h (P < 0.01) and 1 h. In addition, immunohistochemical stain displayed rh‐IFNα2a‐NGR was predominantly located in tumor vascular tissues.
Conclusions
rh‐IFNα2a‐NGR could be an agent for tumor vascular‐targeting therapy and these findings provided references for further clinical study.</description><subject>Angiogenesis Inhibitors - administration & dosage</subject><subject>Angiogenesis Inhibitors - blood</subject><subject>Angiogenesis Inhibitors - pharmacokinetics</subject><subject>Angiogenesis Inhibitors - urine</subject><subject>Animals</subject><subject>Bile - metabolism</subject><subject>Drug Delivery Systems</subject><subject>Drugs, Investigational - administration & dosage</subject><subject>Drugs, Investigational - metabolism</subject><subject>Drugs, Investigational - pharmacokinetics</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Interferon-alpha - administration & dosage</subject><subject>Interferon-alpha - genetics</subject><subject>Interferon-alpha - metabolism</subject><subject>Interferon-alpha - pharmacokinetics</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Models, Biological</subject><subject>Neoplasm Transplantation</subject><subject>NGR</subject><subject>Oligopeptides - administration & dosage</subject><subject>Oligopeptides - chemistry</subject><subject>Oligopeptides - genetics</subject><subject>Oligopeptides - metabolism</subject><subject>pharmacokinetic</subject><subject>Plasmacytoma - blood supply</subject><subject>Plasmacytoma - metabolism</subject><subject>Plasmacytoma - pathology</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recombinant Fusion Proteins - administration & dosage</subject><subject>Recombinant Fusion Proteins - blood</subject><subject>Recombinant Fusion Proteins - pharmacokinetics</subject><subject>Recombinant Fusion Proteins - urine</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Recombinant Proteins - blood</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Recombinant Proteins - pharmacokinetics</subject><subject>Recombinant Proteins - urine</subject><subject>rh-IFNα2a</subject><subject>targeted therapy</subject><subject>Tissue Distribution</subject><subject>tumour</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kU1OHDEQha0oKEwgmxwg8jKK1MQ_3bZ7GY0yAwgNEIGytDzuatrQf9huyJwiZ8lFcqZ4MoCyijclP331VHoPofeUHNH0Pt-OzXhEGWHsFZoxkrNM0kK9RjOSpIwXku-jtyHcEkKkEOIN2mc8V0oqOUM_50M3Gm-iewA8NsZ3xg53rofobMBDjQ2OUzdMPovG3yS1v8GxAW_GDbamr1xlImDfZCeL1e9fzGSr5Tf86GLzj4ZN1bnehQgeKuz66M0D9MMU2k364c5ZwMkKpyvCIdqrTRvg3dM8QNeLr1fz4-zsfHky_3KWWU4Vy0S-Lq2FHEpJAeq6AqbK0tZCSSJkXqQQ1rSsrbCWMGlKAopzU1lWWCuEXPMD9HHnO_rhfoIQdeeChbY1PaTLNOVUKi6kKhP6aYdaP4Tgodajd53xG02J3hagtwXovwUk-MOT77TuoHpBnxNPAN0Bj66FzX-s9OnF8cWzabbb2Wb442XH-DstJJeF_r5a6sXpUl1eXnFN-B-iK6Nu</recordid><startdate>201304</startdate><enddate>201304</enddate><creator>Wang, Xue-Xi</creator><creator>Lu, Li</creator><creator>Song, Chun-Li</creator><creator>Qian, Wei-Na</creator><creator>Zhang, Sheng-Yan</creator><creator>Zhang, Ying-Qi</creator><creator>Wu, Yong-Jie</creator><general>Blackwell Publishing Ltd</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>7X8</scope></search><sort><creationdate>201304</creationdate><title>Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a-NGR with rh-IFNα2a administered intravenously in mice and rats</title><author>Wang, Xue-Xi ; Lu, Li ; Song, Chun-Li ; Qian, Wei-Na ; Zhang, Sheng-Yan ; Zhang, Ying-Qi ; Wu, Yong-Jie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3182-64b9cce4e971eeffde2899cf68706745042b19fc6cc027a90e833adc25cc667b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Angiogenesis Inhibitors - administration & dosage</topic><topic>Angiogenesis Inhibitors - blood</topic><topic>Angiogenesis Inhibitors - pharmacokinetics</topic><topic>Angiogenesis Inhibitors - urine</topic><topic>Animals</topic><topic>Bile - metabolism</topic><topic>Drug Delivery Systems</topic><topic>Drugs, Investigational - administration & dosage</topic><topic>Drugs, Investigational - metabolism</topic><topic>Drugs, Investigational - pharmacokinetics</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Interferon-alpha - administration & dosage</topic><topic>Interferon-alpha - genetics</topic><topic>Interferon-alpha - metabolism</topic><topic>Interferon-alpha - pharmacokinetics</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Models, Biological</topic><topic>Neoplasm Transplantation</topic><topic>NGR</topic><topic>Oligopeptides - administration & dosage</topic><topic>Oligopeptides - chemistry</topic><topic>Oligopeptides - genetics</topic><topic>Oligopeptides - metabolism</topic><topic>pharmacokinetic</topic><topic>Plasmacytoma - blood supply</topic><topic>Plasmacytoma - metabolism</topic><topic>Plasmacytoma - pathology</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Recombinant Fusion Proteins - administration & dosage</topic><topic>Recombinant Fusion Proteins - blood</topic><topic>Recombinant Fusion Proteins - pharmacokinetics</topic><topic>Recombinant Fusion Proteins - urine</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Recombinant Proteins - blood</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Recombinant Proteins - pharmacokinetics</topic><topic>Recombinant Proteins - urine</topic><topic>rh-IFNα2a</topic><topic>targeted therapy</topic><topic>Tissue Distribution</topic><topic>tumour</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xue-Xi</creatorcontrib><creatorcontrib>Lu, Li</creatorcontrib><creatorcontrib>Song, Chun-Li</creatorcontrib><creatorcontrib>Qian, Wei-Na</creatorcontrib><creatorcontrib>Zhang, Sheng-Yan</creatorcontrib><creatorcontrib>Zhang, Ying-Qi</creatorcontrib><creatorcontrib>Wu, Yong-Jie</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>MEDLINE - Academic</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xue-Xi</au><au>Lu, Li</au><au>Song, Chun-Li</au><au>Qian, Wei-Na</au><au>Zhang, Sheng-Yan</au><au>Zhang, Ying-Qi</au><au>Wu, Yong-Jie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a-NGR with rh-IFNα2a administered intravenously in mice and rats</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2013-04</date><risdate>2013</risdate><volume>65</volume><issue>4</issue><spage>574</spage><epage>581</epage><pages>574-581</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><abstract>Objectives
rh‐IFNα2a‐NGR is a promising anti‐tumor candidate. The aim of present study was to compare pharmacokinetics of rh‐IFNα2a‐NGR with rh‐IFNα2a.
Methods
Pharmacokinetics and elimination were investigated after intravenous administration to mice and rats. Compared tumor and tissue distribution profiles between rh‐IFNα2a‐NGR and rh‐IFNα2a were illustrated in the tumor transplanted mice of SP2/0 myeloma. Double antibody sandwich ELISA method was used to assess the level of both rh‐IFNα2a‐NGR and rh‐IFNα2a in serum, tissue, bile and urine.
Key findings
After a single intravenous administration, the pharmacokinetic characters of rh‐IFNα2a‐NGR and rh‐IFNα2a were described using a two‐compartment model. No significant differences were observed between the two drugs in pharmacokinetic and elimination data. However, the concentration of rh‐IFNα2a‐NGR in tumor was 5.34 times and 1.52 times as high as that of rh‐IFNα2a at 0.5 h (P < 0.01) and 1 h. In addition, immunohistochemical stain displayed rh‐IFNα2a‐NGR was predominantly located in tumor vascular tissues.
Conclusions
rh‐IFNα2a‐NGR could be an agent for tumor vascular‐targeting therapy and these findings provided references for further clinical study.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23488787</pmid><doi>10.1111/jphp.12022</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of pharmacy and pharmacology, 2013-04, Vol.65 (4), p.574-581 |
| issn | 0022-3573 2042-7158 |
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| source | Oxford Journals Online |
| subjects | Angiogenesis Inhibitors - administration & dosage Angiogenesis Inhibitors - blood Angiogenesis Inhibitors - pharmacokinetics Angiogenesis Inhibitors - urine Animals Bile - metabolism Drug Delivery Systems Drugs, Investigational - administration & dosage Drugs, Investigational - metabolism Drugs, Investigational - pharmacokinetics Humans Injections, Intravenous Interferon-alpha - administration & dosage Interferon-alpha - genetics Interferon-alpha - metabolism Interferon-alpha - pharmacokinetics Mice Mice, Inbred Strains Models, Biological Neoplasm Transplantation NGR Oligopeptides - administration & dosage Oligopeptides - chemistry Oligopeptides - genetics Oligopeptides - metabolism pharmacokinetic Plasmacytoma - blood supply Plasmacytoma - metabolism Plasmacytoma - pathology Random Allocation Rats Rats, Sprague-Dawley Recombinant Fusion Proteins - administration & dosage Recombinant Fusion Proteins - blood Recombinant Fusion Proteins - pharmacokinetics Recombinant Fusion Proteins - urine Recombinant Proteins - administration & dosage Recombinant Proteins - blood Recombinant Proteins - genetics Recombinant Proteins - metabolism Recombinant Proteins - pharmacokinetics Recombinant Proteins - urine rh-IFNα2a targeted therapy Tissue Distribution tumour |
| title | Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a-NGR with rh-IFNα2a administered intravenously in mice and rats |
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