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Tissue Concentration of Dodecafluoropentane (DDFP) Following Repeated IV Administration in the New Zealand White Rabbit

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Abstract

IV injection of dodecafluoropentane emulsion (DDFPe) increases oxygen transportation and reduces brain infarct volume in a rabbit stroke model. Tissue distribution of the parent perfluorocarbon dodecafluoropentane (DDFP) is unknown but is critical to understanding the mechanism by which DDFPe is effective in treating ischemia and for determining safe dosing. Previous studies showed a DDFP blood half-life of <2 min yet therapeutic effects lasted >90 min after injection. We describe DDFP distribution in brain, kidney, liver, spleen, and lung following nine dosing regimens in New Zealand White (NZW) rabbits. Single and multi-dose schedules were administered to NZW rabbits (n = 27). A single DDFPe dose (0.6 ml/kg) group was sacrificed 2 min after dosing and eight multi-dose groups (4 doses of 0.3 or 0.6 ml/kg and 15 doses of 0.1, 0.3, or 0.6) were sacrificed 90 min after final injections. Tissues were flash frozen and analyzed with headspace sampling/GC-MS. DDFP brain concentration increased with increasing dose in the 15 dose groups (4.70, 8.34, and 14.3 μg/g) and indicative of linear pharmacokinetics within this dose range. The DDFP lung concentration was not reflective of increasing dose or dose frequency. The total clearance of DDFP was consistent with previous reports showing 98% of DDFP is cleared within 2 h of administration.

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Acknowledgments

Sponsored by UAMS Hornick Foundation for Research in Stroke and Related Disorders. The headspace analyzer was kindly provided by the UAMS Center for Translational Neuroscience (NIGMS IDeA Award P30 GM110702). The DDFPe was provided by NuvOx Pharma, Tucson, AZ.

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Authors and Affiliations

  1. Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA

    Christine Arthur, William Culp, Aliza Brown, Michael Borrelli & Robert Skinner

  2. College of Pharmacy, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham Street #622, Little Rock, Arkansas, 72205, USA

    Lin Song, Michael Borrelli & Howard Hendrickson

  3. Department of Neurobiology and Developmental Sciences and Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA

    Robert Skinner

Authors
  1. Christine Arthur
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  2. Lin Song
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  3. William Culp
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  4. Aliza Brown
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  5. Michael Borrelli
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  6. Robert Skinner
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  7. Howard Hendrickson
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Corresponding author

Correspondence to Howard Hendrickson.

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Conflict of Interest

Drs. Culp and Skinner have a patent pending on DDFPe usage in stroke.

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Arthur, C., Song, L., Culp, W. et al. Tissue Concentration of Dodecafluoropentane (DDFP) Following Repeated IV Administration in the New Zealand White Rabbit. AAPS J 19, 520–526 (2017). https://doi.org/10.1208/s12248-016-0013-0

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  • DOI: https://doi.org/10.1208/s12248-016-0013-0

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