Abstract T P93: Blood Pharmacokinetics Of Dodecafluoropentane Following Administration Of Dodecafluoropentane Emulsion To Rabbits

Abstract

Objective: Intravenous injection of Dodecafluoropentane emulsion (DDFPe) increases oxygen transportation and reduces brain infarct volume in rabbit stroke models. Many potential applications in stroke, blood loss, ischemic states, and high risk angiography are yet undefined. Previous studies suggested a blood elimination half-life of <2 min but therapeutic effects last >90 min after injection. In this report, we show a two-phase DDFP pharmacokinetic profile with rapid distribution and longer elimination half-life. Methods: New Zealand White rabbits (N=6) were administered an I.V. bolus of DDFPe (12 mg DDFP/kg). Blood samples were taken at pre-dose and then every 3-min for 40 min following the dose. Samples were transferred to headspace vials and stored at -20 0C until analyzed by headspace sampling coupled to GC-MS analysis. Pharmacokinetic parameters were determined using compartmental analysis with exponential terms calculated using the curve-stripping method (PK Solutions 2.0). Results: A 2-compartment model was the best fit to the DDFP blood concentration-time profiles in each of the animals tested. A rapid distribution phase followed by a longer elimination phase was observed. The distribution phase half-life was 1.15 ± 0.6 min, while the elimination half-life was 13.5 ± 11 min (N=4). Conclusions: A traditional serum pharmacokinetic approach toward development of proper dosing regimens for DDFPe stroke therapy is not feasible given the short half-life relative to the known pharmacodynamic model that shows efficacy for 90-min following a dose of DDFPe. Organ specific pharmacokinetics of DDFP in tissues such as the brain will likely lead to more effective pharmacokinetic models of DDFP following administration of DDFPe.