RATIONALE AND OBJECTIVES: 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.
RATIONALE AND OBJECTIVES: 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.
Authors: Rachel C Stewart; Amit N Patwa; Hrvoje Lusic; Jonathan D Freedman; Michel Wathier; Brian D Snyder; Ali Guermazi; Mark W Grinstaff Journal: J Med Chem Date: 2017-06-27 Impact factor: 7.446
Authors: Benjamin M Yeh; Paul F FitzGerald; Peter M Edic; Jack W Lambert; Robert E Colborn; Michael E Marino; Paul M Evans; Jeannette C Roberts; Zhen J Wang; Margaret J Wong; Peter J Bonitatibus Journal: Adv Drug Deliv Rev Date: 2016-09-09 Impact factor: 15.470
Authors: Paul F FitzGerald; Matthew D Butts; Jeannette C Roberts; Robert E Colborn; Andrew S Torres; Brian D Lee; Benjamin M Yeh; Peter J Bonitatibus Journal: Invest Radiol Date: 2016-12 Impact factor: 6.016
Authors: Connor A Wathen; Nathan Foje; Tony van Avermaete; Bernadette Miramontes; Sarah E Chapaman; Todd A Sasser; Raghuraman Kannan; Steven Gerstler; W Matthew Leevy Journal: Sensors (Basel) Date: 2013-05-27 Impact factor: 3.576