GE-145, a new low-osmolar dimeric radiographic contrast medium.
BACKGROUND
Contrast-induced nephrotoxicity is a significant risk when using radiographic contrast media clinically, especially in high risk patients. Consequently, there is a need for a new contrast agent with improved clinical safety with regards to nephrotoxicity.


OBJECTIVE
To evaluate the physicochemical properties as well as the preclinical safety and biodistribution parameters of the newly developed radiographic contrast medium GE-145.


METHODS
Standard methods for radiographic contrast media were used for evaluation of physicochemical properties. The acute toxicity in rats was studied at 8, 10, and 12.5 gI/kg, the clinical chemistry parameters were determined, and histology of the kidneys was performed. Biodistribution was studied in rats using ¹²³I-labeled GE-145.


RESULTS
GE-145 is more hydrophilic than iodixanol and has a considerably lower osmolality. The viscosity is similar to that of iodixanol and the protein binding is low. The acute toxicity is similar to that of iodixanol and the biodistribution is similar to that of other radiographic contrast media, showing mainly renal excretion. Kidney histology showed a moderate reversible vacuolization, similar to that of iodixanol.


CONCLUSIONS
GE-145 exhibits similar preclinical properties to other dimeric radiographic contrast media. In addition, the low osmolality enables an iso-osmolar formulation containing a significantly higher concentration of electrolytes than Visipaque.
Wistrand
Lars-G
LG
GE Healthcare AS, Medical Diagnostics, Nydalen, Oslo, Norway. lars-goeran.wistrand@ge.com
Rogstad
Astri
A
Hagelin
Gunnar
G
Roed
Line
L
Oulie
Inger
I
Gram
Andreas
A
Evans
Paul
P
Rasmussen
Henrik
H
Grant
Derek
D
Iveson
Peter
P
Newton
Ben
B
Thaning
Mikkel
M
D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000633:toxicity*; D005559:Formamides / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D009994:Osmolar Concentration; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014283:Triiodobenzoic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D014783:Viscosity
C553686:5-(formyl-(3-(formyl-(3,5-bis (2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodophenyl) amino)-2-hydroxypropyl)amino)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide; D003287:Contrast Media; D005559:Formamides; D014283:Triiodobenzoic Acids; C044834:iodixanol