Meglumine gadopentetate 0.5mmol/ml solution for injection 15ml vials

Purpose To compare the long-term brain elimination kinetics and gadolinium species in healthy rats after repeated injections of the contrast agents gadodiamide (a linear contrast agent) or gadoterate (a macrocyclic contrast agent). Materials and Methods Nine-week-old rats received five doses of 2.4 mmol gadolinium per kilogram of body weight over 5 weeks and were followed for 12 months with T1-weighted MRI (n = 140 rats, corresponding to seven time points, two contrast agents, and 10 rats per group). Animals were sacrificed at 1 week, 1 month, and 2, 3, 4, 5, and 12 months after the last injection. Brain and plasma were sampled to determine the total gadolinium concentration by using inductively coupled plasma mass spectrometry (ICP-MS). For the cerebellum, gadolinium speciation analysis was performed after mild extraction at four time points (1 month and 3, 5, and 12 months after the last injection) by using size exclusion chromatography and hydrophilic interaction liquid chromatography, both coupled to ICP-MS. Tissue gadolinium kinetics were fitted to estimate the area under the curves and tissue elimination half-lives over the 12-month injection-free period. Results T1 hyperintensity of the deep cerebellar nuclei was observed only in gadodiamide-treated rats and remained stable from the 1st month after the last injection (the ratio of the signal intensity of the deep cerebellar nuclei to the signal intensity of the brain stem at 1 year: 1.101 ± 0.023 vs 1.037 ± 0.022 before injection, P < .001). Seventy-five percent of the total gadolinium detected after the last injection of gadodiamide (3.25 nmol/g ± 0.30) was retained in the cerebellum at 1 year (2.45 nmol/g ± 0.35), with binding of soluble gadolinium to macromolecules. No T1 hyperintensity was observed with gadoterate, consistent with a rapid, time-dependent washout of the intact gadolinium chelate down to background levels (0.07 nmol/g ± 0.03). Conclusion After repeated administration of gadodiamide, a large portion of gadolinium was retained in the brain, with binding of soluble gadolinium to macromolecules. After repeated injection of gadoterate, only traces of the intact chelated gadolinium were observed with time-dependent clearance. Online supplemental material is available for this article.

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AimThe aim of this review was to evaluate the safety profile of gadoterate meglumine from published literature and pharmacovigilance reports of adverse drug reactions (ADRs) encompassing 35 years of clinical use and more than 170 million administered doses.Materials and methodsA review of published literature up to December 31, 2024 was performed through a search in Embase and PubMed databases. The analysis focused on current safety concerns associated with gadolinium-based contrast agents, the hypersensitivity reactions (HSRs), nephrogenic systemic fibrosis (NSF), gadolinium accumulation, and symptoms associated with gadolinium exposure.ResultsA total of 62 publications reporting safety results for gadoterate meglumine were included. Age ranged from a few weeks to 103 years, including patients with all stages of renal impairment. The incidence of HSRs was reported in 17 studies and ranged from ConclusionsClinical evidence from the published data and pharmacovigilance monitoring demonstrated that gadoterate meglumine is a safe magnetic resonance imaging contrast agent for all age groups in a variety of approved indications throughout the whole body, including in patients with renal impairment.

Abstract licence: CC BY-NC-ND