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?

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). 15 male Crl:C...

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Bibliographic Details
Published in:British journal of radiology 2015-04, Vol.88 (1048), p.20140526-20140526
Main Authors: Kirchin, M A, Lorusso, V, Pirovano, G
Format: Article
Language:English
Subjects:
Animals
Bile - chemistry
Chromatography, High Pressure Liquid
Contrast Media - pharmacokinetics
Disease Models, Animal
Ions
Kidney - metabolism
Liver - metabolism
Male
Meglumine - analogs & derivatives
Meglumine - pharmacokinetics
Nephrogenic Fibrosing Dermopathy - chemically induced
Organometallic Compounds - pharmacokinetics
Other
Rats
Urine - chemistry
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Summary: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). 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. 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. Compensatory elimination may be an effective means to overcome compromised renal or hepatobiliary elimination. The absence of NSF in at-risk patients administered with gadobenate dimeglumine may in part reflect greater Gd(3+) elimination via the hepatobiliary route.
ISSN:0007-1285
1748-880X
DOI:10.1259/bjr.20140526