Peringatan Keamanan

There are no available data on gadopiclenol use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. The available human data on GBCA exposure during pregnancy and adverse fetal outcomes are limited and inconclusive.L49866

In animal reproduction studies, there were no adverse developmental effects observed in rats or rabbits with intravenous administration of gadopiclenol during organogenesis. Because of the potential risks of gadolinium to the fetus, use gadopiclenol only if imaging is essential during pregnancy and cannot be delayed.L49866

In subjects that received a single intravenous dose of gadopiclenol (0.3 mmol/kg) that corresponded to 6 times the recommended dose, headache and nausea were the most frequently reported adverse reactions. Gadopiclenol can be removed from the body by hemodialysis.L43817 Carcinogenicity studies of gadopiclenol have not been performed. Gadopiclenol showed no evidence of mutagenicity in in vitro and in vivo assays. An in vivo study performed in rats showed that up to 10 mmol/kg (62 times the recommended human dose), gadopiclenol did not affect fertility and general reproductive performance.L43817

Gadopiclenol

DB17084

small molecule approved

Deskripsi

Gadopiclenol is a gadolinium-based contrast agent (GBCA) based on a pyclen macrocyclic structure. It is indicated for use with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system and the body.L43817 In 2006, the use of GBCAs was associated with the development of nephrogenic systemic fibrosis (NSF), a rare disorder characterized by the thickening and hardening of skin and subcutaneous tissues. However, studies revealed that NSF was associated with linear GBCAs, not macrocyclic GBCAs, such as gadopiclenol.A254002 Gadopiclenol has high kinetic stability and a high r1 relaxivity, allowing it to be used at lower doses than classic extracellular GBCAs.A254002,A254017

In September 2022, the use of gadopiclenol was approved by the FDA. The product label includes a black box warning regarding the increased risk for NSF among patients with impaired elimination of the drugs.L43817

Struktur Molekul 2D

Berat 970.1
Wujud liquid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Gadopiclenol has a mean elimination half-life of is 1.5 hours.[L43817]
Volume Distribusi At steady state, the mean volume of distribution of gadopiclenol is 13 L.[L43817]
Klirens (Clearance) Gadopiclenol has a total body clearance of 100 mL/min and a renal clearance of 81 mL/min.[L43817]

Absorpsi

At a dose range between 0.025 mmol/kg and 0.3 mmol/kg (0.5 times to 6 times the recommended dosage), the Cmax and AUCinf of gadopiclenol increases in a dose-proportional manner. At the recommended dose, gadopiclenol has a Cmax of 525 µg/mL and an AUCinf of 569 µg·h/mL.L43817 A study that evaluated the pharmacokinetic parameters of gadopiclenol in healthy subjects and patients with brain lesions did not detect significant differences between the two groups.A254007

Metabolisme

Gadopiclenol is not metabolized and is eliminated unchanged.A254002,L43817

Rute Eliminasi

Gadopiclenol is mainly excreted in urine by glomerular filtration. Within 48 hours after administration, approximately 98% of the gadopiclenol dose was recovered in urine.L43817

Interaksi Obat

0 Data
Tidak ada data.

Referensi & Sumber

Synthesis reference: Paratian, JM, et al. (2022) Method for synthesising 2-bromoglutaric acid diesters (French). World Intellectual Property Organization, patent WO 2022/013440 A1. Available at https://patentimages.storage.googleapis.com/64/55/8c/d1f4f75a85a7d8/WO2022013440A1.pdf
Artikel (PubMed)
  • PMID: 30973459
    Robic C, Port M, Rousseaux O, Louguet S, Fretellier N, Catoen S, Factor C, Le Greneur S, Medina C, Bourrinet P, Raynal I, Idee JM, Corot C: Physicochemical and Pharmacokinetic Profiles of Gadopiclenol: A New Macrocyclic Gadolinium Chelate With High T1 Relaxivity. Invest Radiol. 2019 Aug;54(8):475-484. doi: 10.1097/RLI.0000000000000563.
  • PMID: 30870257
    Hao J, Bourrinet P, Desche P: Assessment of Pharmacokinetic, Pharmacodynamic Profile, and Tolerance of Gadopiclenol, A New High Relaxivity GBCA, in Healthy Subjects and Patients With Brain Lesions (Phase I/IIa Study). Invest Radiol. 2019 Jul;54(7):396-402. doi: 10.1097/RLI.0000000000000556.
  • PMID: 32776767
    Lancelot E, Raynaud JS, Desche P: Current and Future MR Contrast Agents: Seeking a Better Chemical Stability and Relaxivity for Optimal Safety and Efficacy. Invest Radiol. 2020 Sep;55(9):578-588. doi: 10.1097/RLI.0000000000000684.

Contoh Produk & Brand

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International Brands
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Sekuens Gen/Protein (FASTA)

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