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Pharmacokinetics of Plasmid DNA in the Rat

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Abstract

Purpose. 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.

Methods. SC, OC, and L pDNA were injected at 2500, 500, 333, and 250 μg doses. The concentrations in the bloodstream of OC and L pDNA were monitored.

Results. SC pDNA was detectable in the bloodstream only after a 2500 μg 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.

Conclusions. 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.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32610

    Brett E. Houk, Robin Martin, Günther Hochhaus & Jeffrey A. Hughes

  2. Department of Pharmaceutics, College of Pharmacy, University of Florida, P.O. Box 100494 JHMHC, Gainesville, FL, 32610

    Jeffrey A. Hughes

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  1. Brett E. Houk
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  2. Robin Martin
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Houk, B.E., Martin, R., Hochhaus, G. et al. Pharmacokinetics of Plasmid DNA in the Rat. Pharm Res 18, 67–74 (2001). https://doi.org/10.1023/A:1011078711008

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