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?

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. CONCLUSION: Compensatory elimination may be an effective means to overcome compromised renal or hepatobiliary elimination. ADVANCES IN KNOWLEDGE: The absence of NSF in at-risk patients administered with gadobenate dimeglumine may in part reflect greater Gd(3+) elimination via the hepatobiliary route.