title: Iosimenol, a low-viscosity nonionic dimer: preclinical physicochemistry, pharmacology, and pharmacokinetics.
abstract: 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.
authors.affiliation: Department of Radiology, University of California, San Diego Medical School, La Jolla, California 92037, USA. radiologyresearch@ucsd.edu
authors.forename: Milos
authors.initials: M
authors.lastname: Sovak
authors.forename: Ron
authors.initials: R
authors.lastname: Terry
authors.forename: Claudia
authors.initials: C
authors.lastname: Abramjuk
authors.forename: Vera
authors.initials: V
authors.lastname: Faberová
authors.forename: Magdalena
authors.initials: M
authors.lastname: Fiserova
authors.forename: Milan
authors.initials: M
authors.lastname: Laznicek
authors.forename: Jost
authors.initials: J
authors.lastname: Leuschner
authors.forename: Jiri
authors.initials: J
authors.lastname: Malinak
authors.forename: Petr
authors.initials: P
authors.lastname: Zahradnik
authors.forename: Ondrej
authors.initials: O
authors.lastname: Masner
authors.forename: Allen
authors.initials: A
authors.lastname: Seligson
mesh_terms: 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
chemical_list: D001549:Benzamides; D003287:Contrast Media; D011412:Propanolamines; D014283:Triiodobenzoic Acids; C044834:iodixanol; C450045:iosmin