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Characterization of continuously extruded iopromide-carrying liposomes for computed tomography blood-pool imaging
1Research Laboratories of Schering Ag, Berlin, Germany. Jens.Leike@Schering.de
Rationale And Objectives:
Contrast-carrying liposomes are potentially useful as computed tomography (CT) blood-pool agents. In the present study, preliminary safety, pharmacokinetics, and the CT imaging behavior of continuously extruded iopromide-carrying liposomes were studied.
Methods:
Iopromide liposomes were prepared by continuous high-pressure extrusion. Cell membrane-damaging characteristics were assessed in vitro in dog erythrocytes. Acute and subchronic toxicity and pharmacokinetics parameters were determined in rats. Computed tomography imaging efficiency was studied in rabbits.
Results:
The iopromide-carrying liposomes caused only minor morphological changes in dog erythrocytes. The median lethal dose in rats was approximately 4.5 g of total iodine per kilogram of body weight. In a subchronic tolerance study in rats that were administered six doses of 1 g iodine per kilogram twice a week, no adverse effects were observed. The pharmacokinetics in rats was dose dependent, and elimination of iopromide was almost complete within 7 days after intravenous administration. In rabbits, at a dose of 300 mg total iodine per kilogram, the iopromide-carrying liposomes displayed prolonged blood circulation, with mean CT density differences > 60 Hounsfield units (aorta) for up to 10 minutes.
Conclusions:
The iopromide liposomes were well tolerated, almost completely excreted, and have potential as a CT blood-pool imaging agent.