Characterization of continuously extruded iopromide-carrying liposomes for computed tomography blood-pool imaging.
OBJECTIVE
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.
Leike
J U
JU
Research Laboratories of Schering Ag, Berlin, Germany. Jens.Leike@Schering.de
Sachse
A
A
Rupp
K
K
D000818:Animals; D001027:Aortography; D001769:Blood; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007472:Iohexol / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity; D008081:Liposomes; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014057:Tomography, X-Ray Computed; D014682:Vena Cava, Inferior / Q000000981:diagnostic imaging
D003287:Contrast Media; D008081:Liposomes; D007472:Iohexol; C038192:iopromide