Tissue Concentration of Dodecafluoropentane (DDFP) Following Repeated IV Administration in the New Zealand White Rabbit
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.
KEY WORDSdodecafluoropentane emulsion GC-MS ischemia rabbit tissue distribution
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.
Compliance with Ethical Standards
Conflict of Interest
Drs. Culp and Skinner have a patent pending on DDFPe usage in stroke.
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