title: Tissue Concentration of Dodecafluoropentane (DDFP) Following Repeated IV Administration in the New Zealand White Rabbit.
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.
authors.affiliation: Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Arthur
authors.affiliation: College of Pharmacy, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham Street #622, Little Rock, Arkansas, 72205, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
authors.forename: William
authors.initials: W
authors.lastname: Culp
authors.affiliation: Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
authors.forename: Aliza
authors.initials: A
authors.lastname: Brown
authors.affiliation: Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.|College of Pharmacy, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham Street #622, Little Rock, Arkansas, 72205, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Borrelli
authors.affiliation: Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.|Department of Neurobiology and Developmental Sciences and Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Skinner
authors.affiliation: College of Pharmacy, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham Street #622, Little Rock, Arkansas, 72205, USA. HowardHendricksonP@uams.edu.
authors.forename: Howard
authors.initials: H
authors.lastname: Hendrickson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007275:Injections, Intravenous; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D014018:Tissue Distribution; D010420:Pentanes
chemical_list: D005466:Fluorocarbons; D018696:Neuroprotective Agents; C008806:perfluoropentane; D010420:Pentanes
keywords: GC-MS; dodecafluoropentane emulsion; ischemia; rabbit; tissue distribution