title: Safety, tolerance, biodistribution, and MR imaging enhancement of the liver with gadobenate dimeglumine: results of clinical pharmacologic and pilot imaging studies in nonpatient and patient volunteers.
abstract: OBJECTIVE
  The purpose of this study was to assess safety, tolerance, biodistribution, and magnetic resonance (MR) imaging enhancement of the liver with gadobenate dimeglumine.
  
  
  METHODS
  Phase I single-blind studies were performed in 53 healthy volunteers, of whom 39 received gadobenate dimeglumine and 14 placebo. Another 106 patients with focal liver disease received gadobenate dimeglumine in parallel-group, open-label, phase II studies. The imaging potential of gadobenate dimeglumine was assessed in all 106 patients plus 11 healthy volunteers, whereas pharmacokinetics were determined for 42 healthy volunteers. Safety was assessed for all subjects enrolled in the study. Imaging protocols for healthy volunteers were similar to those for patients and comprised predose T2-weighted sequences and pre- and postinjection T1-weighted spin-echo and gradient-echo sequences.
  
  
  RESULTS
  Gadobenate dimeglumine was safe and well tolerated in healthy volunteers and patients, with pharmacokinetics described adequately as a distribution phase and an elimination phase. Most of the injected dose of gadobenate was excreted unchanged in urine within 24 hours, although a fraction corresponding to 0.6%-4.0% of the injected dose was eliminated with the bile and recovered in the feces. The gadobenate dimeglumine-enhanced signal intensity of liver parenchyma was dose-related and constant for 120 minutes. Gadobenate dimeglumine-enhanced MR imaging was superior to nonenhanced MR imaging in more than 50% of patient studies, with more lesions seen in 26%-38% of patients and smaller lesions in 21%-33% of patients. In general, image sets acquired 40-180 minutes after administration of a dose were preferred, whereas images acquired during the dynamic phase after administration were typical of those obtained with extracellular fluid contrast agents.
  
  
  CONCLUSIONS
  Gadobenate dimeglumine is a safe and efficacious MR imaging contrast agent suitable for both delayed and dynamic imaging of the liver.
authors.affiliation: Medical and Regulatory Affairs, Bracco SpA, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Spinazzi
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: G
authors.initials: G
authors.lastname: Pirovano
authors.forename: M
authors.initials: M
authors.lastname: Kirchin
mesh_terms: D000328:Adult; D000368:Aged; D003287:Contrast Media / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008099:Liver / Q000033:anatomy & histology* / Q000473:pathology*; D008107:Liver Diseases / Q000175:diagnosis; D008113:Liver Neoplasms / Q000175:diagnosis / Q000556:secondary; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008536:Meglumine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000493:pharmacokinetics*; D010865:Pilot Projects; D016037:Single-Blind Method
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine