Pharmacokinetics of plasmid DNA in the rat
The pharmacokinetics of plasmid DNA after IV bolus administration in the rat by following supercoiled (SC), open circular (OC), and linear (L) pDNA forms of the plasmid. SC, OC, and L pDNA were injected at 2,500, 500, 333, and 250 microg doses. The concentrations in the bloodstream of OC and L pDNA...
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| Veröffentlicht in: | Pharmaceutical research 2001, Vol.18 (1), p.67-74 |
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| creator | HOUK, Brett E MARTIN, Robin HOCHHAUS, Günther HUGHES, Jeffrey A |
| description | The pharmacokinetics of plasmid DNA after IV bolus administration in the rat by following supercoiled (SC), open circular (OC), and linear (L) pDNA forms of the plasmid.
SC, OC, and L pDNA were injected at 2,500, 500, 333, and 250 microg doses. The concentrations in the bloodstream of OC and L pDNA were monitored.
SC pDNA was detectable in the bloodstream only after a 2,500 microg dose, and had a clearance of 390(+/-50) ml/min and Vd of 81(+/-8) ml. The pharmacokinetics of OC pDNA exhibited non-linear characteristics with clearance ranging from 8.3(+/-0.8) to 1.3(+/-0.2) ml/min and a Vd of 39(+/-19) ml. L pDNA was cleared at 7.6(+/-2.3) ml/min and had a Vd of 37(+/-17) ml. AUC analysis revealed that 60(+/-10) % of the SC was converted to the OC form, and nearly complete conversion of the OC pDNA to L pDNA. Clearance of SC pDNA was decreased after liposome complexation to 87(+/-30) ml/min. However the clearance of OC and L pDNA was increased relative to naked pDNA at an equivalent dose to 37(+/-9) ml/min and 95(+/-37) ml/min respectively.
SC pDNA is rapidly metabolized and cleared from the circulation. OC pDNA displays non-linear pharmacokinetics. Linear pDNA exhibits first order kinetics. Liposome complexation protects the SC topoform, but the complexes are more rapidly cleared than the naked pDNA. |
| doi_str_mv | 10.1023/A:1011078711008 |
| format | Article |
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SC, OC, and L pDNA were injected at 2,500, 500, 333, and 250 microg doses. The concentrations in the bloodstream of OC and L pDNA were monitored.
SC pDNA was detectable in the bloodstream only after a 2,500 microg dose, and had a clearance of 390(+/-50) ml/min and Vd of 81(+/-8) ml. The pharmacokinetics of OC pDNA exhibited non-linear characteristics with clearance ranging from 8.3(+/-0.8) to 1.3(+/-0.2) ml/min and a Vd of 39(+/-19) ml. L pDNA was cleared at 7.6(+/-2.3) ml/min and had a Vd of 37(+/-17) ml. AUC analysis revealed that 60(+/-10) % of the SC was converted to the OC form, and nearly complete conversion of the OC pDNA to L pDNA. Clearance of SC pDNA was decreased after liposome complexation to 87(+/-30) ml/min. However the clearance of OC and L pDNA was increased relative to naked pDNA at an equivalent dose to 37(+/-9) ml/min and 95(+/-37) ml/min respectively.
SC pDNA is rapidly metabolized and cleared from the circulation. OC pDNA displays non-linear pharmacokinetics. Linear pDNA exhibits first order kinetics. Liposome complexation protects the SC topoform, but the complexes are more rapidly cleared than the naked pDNA.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/A:1011078711008</identifier><identifier>PMID: 11336355</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Alcohol ; Animals ; Area Under Curve ; Biological and medical sciences ; DNA, Circular - blood ; DNA, Circular - pharmacokinetics ; DNA, Superhelical - blood ; DNA, Superhelical - pharmacokinetics ; General pharmacology ; Lipids ; Lipids - pharmacokinetics ; Liposomes - pharmacokinetics ; Male ; Medical sciences ; Models, Biological ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacokinetics ; Pharmacology. Drug treatments ; Phenols ; Plasmids - blood ; Plasmids - pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution - physiology ; Veins & arteries</subject><ispartof>Pharmaceutical research, 2001, Vol.18 (1), p.67-74</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Jan 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c308t-f22d76173ccdbd8a411d04d684bdd5ecdc815bad454a1576f352de00c0d9b65e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=987215$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11336355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HOUK, Brett E</creatorcontrib><creatorcontrib>MARTIN, Robin</creatorcontrib><creatorcontrib>HOCHHAUS, Günther</creatorcontrib><creatorcontrib>HUGHES, Jeffrey A</creatorcontrib><title>Pharmacokinetics of plasmid DNA in the rat</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>The pharmacokinetics of plasmid DNA after IV bolus administration in the rat by following supercoiled (SC), open circular (OC), and linear (L) pDNA forms of the plasmid.
SC, OC, and L pDNA were injected at 2,500, 500, 333, and 250 microg doses. The concentrations in the bloodstream of OC and L pDNA were monitored.
SC pDNA was detectable in the bloodstream only after a 2,500 microg dose, and had a clearance of 390(+/-50) ml/min and Vd of 81(+/-8) ml. The pharmacokinetics of OC pDNA exhibited non-linear characteristics with clearance ranging from 8.3(+/-0.8) to 1.3(+/-0.2) ml/min and a Vd of 39(+/-19) ml. L pDNA was cleared at 7.6(+/-2.3) ml/min and had a Vd of 37(+/-17) ml. AUC analysis revealed that 60(+/-10) % of the SC was converted to the OC form, and nearly complete conversion of the OC pDNA to L pDNA. Clearance of SC pDNA was decreased after liposome complexation to 87(+/-30) ml/min. However the clearance of OC and L pDNA was increased relative to naked pDNA at an equivalent dose to 37(+/-9) ml/min and 95(+/-37) ml/min respectively.
SC pDNA is rapidly metabolized and cleared from the circulation. OC pDNA displays non-linear pharmacokinetics. Linear pDNA exhibits first order kinetics. Liposome complexation protects the SC topoform, but the complexes are more rapidly cleared than the naked pDNA.</description><subject>Alcohol</subject><subject>Animals</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>DNA, Circular - blood</subject><subject>DNA, Circular - pharmacokinetics</subject><subject>DNA, Superhelical - blood</subject><subject>DNA, Superhelical - pharmacokinetics</subject><subject>General pharmacology</subject><subject>Lipids</subject><subject>Lipids - pharmacokinetics</subject><subject>Liposomes - pharmacokinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenols</subject><subject>Plasmids - blood</subject><subject>Plasmids - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Tissue Distribution - physiology</subject><subject>Veins & arteries</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpd0MtLxDAQBvAgiruunr1JUfAgVGfyaFJvy_qERT0oeCtpkrJZ-1ib9uB_b8DVg5eZy4-Pb4aQY4RLBMqu5tcIiCCVjBPUDpmikCzNgb_vkilIylMlOU7IQQhriAJzvk8miIxlTIgpuXhZ6b7RpvvwrRu8CUlXJZtah8bb5OZpnvg2GVYu6fVwSPYqXQd3tN0z8nZ3-7p4SJfP94-L-TI1DNSQVpRamaFkxtjSKs0RLXCbKV5aK5yxRqEoteWC61g2q5ig1gEYsHmZCcdm5Pwnd9N3n6MLQ9H4YFxd69Z1YygkKKpAsQhP_8F1N_Zt7FZQSiVk8cSITrZoLBtni03vG91_Fb8viOBsC3Qwuq563Rof_lyuJEXBvgF0CWel</recordid><startdate>2001</startdate><enddate>2001</enddate><creator>HOUK, Brett E</creator><creator>MARTIN, Robin</creator><creator>HOCHHAUS, Günther</creator><creator>HUGHES, Jeffrey A</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>2001</creationdate><title>Pharmacokinetics of plasmid DNA in the rat</title><author>HOUK, Brett E ; MARTIN, Robin ; HOCHHAUS, Günther ; HUGHES, Jeffrey A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c308t-f22d76173ccdbd8a411d04d684bdd5ecdc815bad454a1576f352de00c0d9b65e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Alcohol</topic><topic>Animals</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>DNA, Circular - blood</topic><topic>DNA, Circular - pharmacokinetics</topic><topic>DNA, Superhelical - blood</topic><topic>DNA, Superhelical - pharmacokinetics</topic><topic>General pharmacology</topic><topic>Lipids</topic><topic>Lipids - pharmacokinetics</topic><topic>Liposomes - pharmacokinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Biological</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenols</topic><topic>Plasmids - blood</topic><topic>Plasmids - pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Tissue Distribution - physiology</topic><topic>Veins & arteries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HOUK, Brett E</creatorcontrib><creatorcontrib>MARTIN, Robin</creatorcontrib><creatorcontrib>HOCHHAUS, Günther</creatorcontrib><creatorcontrib>HUGHES, Jeffrey A</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HOUK, Brett E</au><au>MARTIN, Robin</au><au>HOCHHAUS, Günther</au><au>HUGHES, Jeffrey A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of plasmid DNA in the rat</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2001</date><risdate>2001</risdate><volume>18</volume><issue>1</issue><spage>67</spage><epage>74</epage><pages>67-74</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>The pharmacokinetics of plasmid DNA after IV bolus administration in the rat by following supercoiled (SC), open circular (OC), and linear (L) pDNA forms of the plasmid.
SC, OC, and L pDNA were injected at 2,500, 500, 333, and 250 microg doses. The concentrations in the bloodstream of OC and L pDNA were monitored.
SC pDNA was detectable in the bloodstream only after a 2,500 microg dose, and had a clearance of 390(+/-50) ml/min and Vd of 81(+/-8) ml. The pharmacokinetics of OC pDNA exhibited non-linear characteristics with clearance ranging from 8.3(+/-0.8) to 1.3(+/-0.2) ml/min and a Vd of 39(+/-19) ml. L pDNA was cleared at 7.6(+/-2.3) ml/min and had a Vd of 37(+/-17) ml. AUC analysis revealed that 60(+/-10) % of the SC was converted to the OC form, and nearly complete conversion of the OC pDNA to L pDNA. Clearance of SC pDNA was decreased after liposome complexation to 87(+/-30) ml/min. However the clearance of OC and L pDNA was increased relative to naked pDNA at an equivalent dose to 37(+/-9) ml/min and 95(+/-37) ml/min respectively.
SC pDNA is rapidly metabolized and cleared from the circulation. OC pDNA displays non-linear pharmacokinetics. Linear pDNA exhibits first order kinetics. Liposome complexation protects the SC topoform, but the complexes are more rapidly cleared than the naked pDNA.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>11336355</pmid><doi>10.1023/A:1011078711008</doi><tpages>8</tpages></addata></record> |
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| subjects | Alcohol Animals Area Under Curve Biological and medical sciences DNA, Circular - blood DNA, Circular - pharmacokinetics DNA, Superhelical - blood DNA, Superhelical - pharmacokinetics General pharmacology Lipids Lipids - pharmacokinetics Liposomes - pharmacokinetics Male Medical sciences Models, Biological Pharmaceutical technology. Pharmaceutical industry Pharmacokinetics Pharmacology. Drug treatments Phenols Plasmids - blood Plasmids - pharmacokinetics Rats Rats, Sprague-Dawley Tissue Distribution - physiology Veins & arteries |
| title | Pharmacokinetics of plasmid DNA in the rat |
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