Iosimenol, a low-viscosity nonionic dimer: preclinical physicochemistry, pharmacology, and pharmacokinetics.
OBJECTIVE
Newer radiologic techniques require fast bolus injections and thus low-viscosity, high-concentration, well-tolerated contrast media (CM), especially in vulnerable patients. To this end, we designed and developed iosimenol, a novel isotonic nonionic dimer, and have conducted tests to enable its clinical evaluation.


METHODS
Standard physicochemical methods were used. Effects on erythrocyte morphology and coagulation were investigated in human and rat blood. Neural tolerance was assessed by behavioral tests in rats after intracisternal injection. Immunosensitizing potential was evaluated by the skin sensitization test in guinea pigs and by the popliteal lymph node assay in rats. Pharmacokinetics and biotransformation were investigated in rats and dogs.


RESULTS
Iosimenol is extremely hydrophilic, it is less viscous than any other isotonic CM, has little effect on erythrocytes and blood coagulation, and has good neural tolerance. No immunosensitizing effect was found in validated animal models. Pharmacokinetics are identical with other angio- and urographic CM.


CONCLUSIONS
Iosimenol is the only CM which, although isotonic, affords, unlike current nonionic dimers, at the same iodine concentration the low viscosity of monomeric, nonionic agents, which are all hypertonic. Iosimenol's pharmacologic characteristics closely resemble those of iotrolan and iodixanol.
Sovak
Milos
M
Department of Radiology, University of California, San Diego Medical School, La Jolla, California 92037, USA. radiologyresearch@ucsd.edu
Terry
Ron
R
Abramjuk
Claudia
C
Faberová
Vera
V
Fiserova
Magdalena
M
Laznicek
Milan
M
Leuschner
Jost
J
Malinak
Jiri
J
Zahradnik
Petr
P
Masner
Ondrej
O
Seligson
Allen
A
D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects; D008297:Male; D009420:Nervous System / Q000187:drug effects; D009994:Osmolar Concentration; D011412:Propanolamines / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D023422:Skin Irritancy Tests; D014018:Tissue Distribution; D014283:Triiodobenzoic Acids / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D014783:Viscosity
D001549:Benzamides; D003287:Contrast Media; D011412:Propanolamines; D014283:Triiodobenzoic Acids; C044834:iodixanol; C450045:iosmin