title: Pharmacokinetics and tissue distribution in animals of gadobenate ion, the magnetic resonance imaging contrast enhancing component of gadobenate dimeglumine 0.5 M solution for injection (MultiHance).
abstract: OBJECTIVE
  Evaluation of the pharmacokinetic behavior of gadobenate dimeglumine, a new multipurpose parenteral contrast agent for magnetic resonance imaging.
  
  
  METHODS
  The pharmacokinetics were evaluated in rats, rabbits, dogs and monkeys after intravenous injections of non-labelled gadobenate dimeglumine and, for biodistribution studies, 153Gd-labelled gadobenate dimeglumine. Assays were performed by high performance liquid chromatography, X-ray fluorescence and gamma spectrometry. The binding of gadobenate ion to animal and human serum albumin was studied by equilibrium dialysis.
  
  
  RESULTS
  After intravenous injection gadobenate dimeglumine distributes into plasma and extracellular fluid as well as into the intrahepatocytic space. Gadobenate ion is cleared from plasma by renal and biliary excretion. It does not accumulate in specific tissues, except temporarily in tissues related to its elimination. Gadobenate ion is not metabolized. Its binding to plasma proteins is too weak to be detected by equilibrium dialysis.
  
  
  CONCLUSIONS
  Gadobenate dimeglumine combines the properties of an extracellular-fluid agent with those of a hepatobiliary agent. Its complete elimination and biological stability satisfy the requirements for its safe use in humans.
authors.affiliation: Milano Research Centre, Bracco SpA, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: T
authors.initials: T
authors.lastname: Arbughi
authors.forename: P
authors.initials: P
authors.lastname: Tirone
authors.forename: C
authors.initials: C
authors.lastname: de Haën
mesh_terms: D000818:Animals; D001345:Autoradiography; D001646:Bile / Q000737:chemistry; D001774:Blood Chemical Analysis; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D004285:Dogs; D005243:Feces / Q000737:chemistry; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013052:Spectrometry, X-Ray Emission; D014018:Tissue Distribution; D014556:Urine / Q000737:chemistry
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine; D005682:Gadolinium