ArticlePharmaceutical research2001
Pharmacokinetics of plasmid DNA in the rat.
Article in Pharmaceutical research, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The trial behind it
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Who cites it
9 citing papers in PubMed.
- Hybrid polymeric-protein nano-carriers (HPPNC) for targeted delivery of TGFβ inhibitors to hepatocellular carcinoma cells.Journal of materials science. Materials in medicine · 2017Article
- Quantitative evaluation of DNA dissociation from liposome carriers and DNA escape from endosomes during lipid-mediated gene delivery.Human gene therapy methods · 2014Article
- Nucleic acid delivery with microbubbles and ultrasound.Advanced drug delivery reviews · 2014Review
- Design and application of multifunctional DNA nanocarriers for therapeutic delivery.Acta biomaterialia · 2014Review
- Engineered biological entities for drug delivery and gene therapy protein nanoparticles.Progress in molecular biology and translational science · 2011Review
- Gene therapy: a pharmacokinetic/pharmacodynamic modelling overview.Pharmaceutical research · 2010Review
- Release of plasmid DNA-encoding IL-10 from PLGA microparticles facilitates long-term reversal of neuropathic pain following a single intrathecal administration.Pharmaceutical research · 2010Article
- Evaluation of pharmacokinetics of bioreducible gene delivery vectors by real-time PCR.Pharmaceutical research · 2009Article
- Cyclic RGD-targeting of reversibly stabilized DNA nanoparticles enhances cell uptake and transfection in vitro.Journal of drug targeting · 2009Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
purposeThe 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.
methodsSC, 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.
resultsSC 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.
conclusionsSC 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.
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Registered trials
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