title: Compensatory biliary and urinary excretion of gadobenate ion after administration of gadobenate dimeglumine (MultiHance(®)) in cases of impaired hepatic or renal function: a mechanism that may aid in the prevention of nephrogenic systemic fibrosis?
abstract: OBJECTIVE
  To determine whether increased elimination of gadobenate ion via the hepatobiliary pathway might compensate for reduced/absent elimination via the urinary pathway in the event of compromised renal function, as a possible protective mechanism against nephrogenic systemic fibrosis (NSF).
  
  
  METHODS
  15 male Crl:CD(®) R(SD)Br rats (Charles River Italia, Como, Italy) randomized to three treatment groups: (1) animals with occluded bile ducts, (2) animals with occluded renal vessels and (3) control animals, each received 0.25 mmol kg(-1) of bodyweight of gadobenate dimeglumine (MultiHance(®); Bracco Imaging SpA, Milan, Italy). Urine and bile were collected from 0-30, 30-60, 60-120, 120-240 and 240-480 min after gadobenate dimeglumine administration prior to exsanguination. Determinations of gadobenate ion in blood, bile and urine were performed by high-performance liquid chromatography. Gadolinium (Gd(3+)) levels in excised liver and kidneys were determined by X-ray fluorescence.
  
  
  RESULTS
  The recovery of gadobenate ion in the urine of rats with bile duct occlusion was significantly higher than that in the urine of normal rats (89.1 ± 4.2% vs 60.6 ± 2.8%; p < 0.0001). Conversely, mean recovery in the bile of rats with renal vessel occlusion was significantly higher than that in the bile of normal rats (96.16 ± 0.55% vs 33.5 ± 4.7%; p < 0.0001). Gadobenate ion was not quantifiable in any group 8 h post-injection.
  
  
  CONCLUSIONS
  Compensatory elimination may be an effective means to overcome compromised renal or hepatobiliary elimination.
  
  
  CONCLUSIONS
  The absence of NSF in at-risk patients administered with gadobenate dimeglumine may in part reflect greater Gd(3+) elimination via the hepatobiliary route.
authors: 1 Global Medical and Regulatory Affairs, Bracco Imaging SpA, Milan, Italy.
authors: M A
authors: MA
authors: Kirchin
authors: V
authors: V
authors: Lorusso
authors: G
authors: G
authors: Pirovano
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D007477:Ions; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D054989:Nephrogenic Fibrosing Dermopathy / Q000139:chemically induced; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D014556:Urine / Q000737:chemistry
chemical_list: D003287:Contrast Media; D007477:Ions; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine
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