Identification
- Summary
Gadopiclenol is a gadolinium-based contrast agent (GBCA) used with contrasted magnetic resonance imaging (MRI) to detect and visualize lesions and abnormal vascularity.
- Brand Names
- Elucirem
- Generic Name
- Gadopiclenol
- DrugBank Accession Number
- DB17084
- Background
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.4 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.1 Gadopiclenol has high kinetic stability and a high r1 relaxivity, allowing it to be used at lower doses than classic extracellular GBCAs.1,3
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.4
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Gadopiclenol (DB17084)
- Weight
- Average: 970.1
Monoisotopic: 970.2919 - Chemical Formula
- C35H54GdN7O15
- Synonyms
- (.alpha.3,.alpha.6,.alpha.9-tris(3-((2,3-dihydroxypropyl)amino)-3-oxopropyl)-3,6,9,15-tetraazabicyclo(9.3.1)pentadeca-1(15),11,13-triene-3,6,9-triacetato(3-)-.kappa.n3,.kappa.n6,.kappa.n9,.kappa.n15,.kappa.o3,.kappa.o6,.kappa.o9)gadolinium
- 2-[3,9-bis[1-carboxylato-4-(2,3-dihydroxypropylamino)-4-oxobutyl]-3,6,9,15-tetrazabicyclo[9.3.1]pentadeca-1(15),11,13-trien-6-yl]-5-(2,3-dihydroxypropylamino)-5-oxopentanoate;gadolinium(3+)
- External IDs
- P-03277
- P03277
Pharmacology
- Indication
Gadopiclenol is indicated in adult and pediatric patients aged 2 years and older for use with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system (brain, spine, and associated tissues) and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system).4
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Cns abnormal vascularity •••••••••••• •••••• ••••••••• ••••••••• Diagnostic agent Abnormal vascularity •••••••••••• •••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
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Variations in radiofrequency signal intensity allow the visualization of normal and pathological tissues during magnetic resonance imaging (MRI). These variations occur due to differences in proton density, differences of the spin-lattice or longitudinal relaxation times (T1), or differences in the spin-spin or transverse relaxation time (T2). Gadopiclenol shortens the T1 and T2 relaxation times and allows the visualization of targeted tissues during an MRI. The extent to which a contrast agent can affect the relaxation rate of tissue water (1/T1 or 1/T2) is termed relaxivity (r1 or r2). Gadopiclenol has a high r1 relaxivity compared to other gadolinium-based contrast agents.3,4 The use of gadopiclenol is not associated with QT interval prolongation; however, it can increase the risk for nephrogenic systemic fibrosis in patients with impaired elimination of the drugs. The use of gadopiclenol may also cause hypersensitivity reactions and acute kidney injury.4
- Mechanism of action
Gadopiclenol is a macrocyclic non-ionic complex of gadolinium and a paramagnetic molecule that develops a magnetic moment when placed in a magnetic field. The magnetic moment alters the relaxation rates of water protons in its vicinity in the body.4 Its use in magnetic resonance imaging (MRI) allows to selectively increase contrast in tissues where gadopiclenol accumulates.4
- Absorption
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.4 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.2
- Volume of distribution
At steady state, the mean volume of distribution of gadopiclenol is 13 L.4
- Protein binding
At clinically relevant concentrations, the protein binding of gadopiclenol is ≤ 1.8%.4
- Metabolism
Gadopiclenol is not metabolized and is eliminated unchanged.1,4
- Route of elimination
Gadopiclenol is mainly excreted in urine by glomerular filtration. Within 48 hours after administration, approximately 98% of the gadopiclenol dose was recovered in urine.4
- Half-life
Gadopiclenol has a mean elimination half-life of is 1.5 hours.4
- Clearance
Gadopiclenol has a total body clearance of 100 mL/min and a renal clearance of 81 mL/min.4
- Adverse Effects
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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.5
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.5
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.4 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.4
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Elucirem (Guerbet)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Elucirem Injection 485.1 mg/1mL Intravenous Guerbet LLC 2022-09-21 Not applicable US 
Elucirem Injection 485.1 mg/1mL Intravenous Guerbet LLC 2022-09-21 Not applicable US Elucirem Injection 485.1 mg/1mL Intravenous Guerbet LLC 2022-09-21 Not applicable US Elucirem Injection 485.1 mg/1mL Intravenous Guerbet LLC 2022-09-21 Not applicable US Elucirem Injection 485.1 mg/1mL Intravenous Guerbet LLC 2022-09-21 Not applicable US
Categories
- ATC Codes
- V08CA12 — Gadopiclenol
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- S276568KOY
- CAS number
- 933983-75-6
- InChI Key
- GNRQMLROZPOLDG-UHFFFAOYSA-K
- InChI
- InChI=1S/C35H57N7O15.Gd/c43-19-24(46)14-36-30(49)7-4-27(33(52)53)40-10-12-41(28(34(54)55)5-8-31(50)37-15-25(47)20-44)17-22-2-1-3-23(39-22)18-42(13-11-40)29(35(56)57)6-9-32(51)38-16-26(48)21-45;/h1-3,24-29,43-48H,4-21H2,(H,36,49)(H,37,50)(H,38,51)(H,52,53)(H,54,55)(H,56,57);/q;+3/p-3
- IUPAC Name
- gadolinium(3+) 2-[6,9-bis({1-carboxylato-3-[(2,3-dihydroxypropyl)carbamoyl]propyl})-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(14),11(15),12-trien-3-yl]-4-[(2,3-dihydroxypropyl)carbamoyl]butanoate
- SMILES
- [Gd+3].OCC(O)CNC(=O)CCC(N1CCN(CC2=CC=CC(CN(CC1)C(CCC(=O)NCC(O)CO)C([O-])=O)=N2)C(CCC(=O)NCC(O)CO)C([O-])=O)C([O-])=O
References
- 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
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- FDA Approved Drug Products: ELUCIREM (gadopiclenol) injection for intravenous use [Link]
- FDA Approved Drug Products: ELUCIREMTM (gadopiclenol) injection, for intravenous use (Jan 2024) [Link]
- External Links
- ChemSpider
- 17350646
- 2618720
- Wikipedia
- Gadopiclenol
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Not Yet Recruiting Diagnostic Prostate Cancer 1 4 Not Yet Recruiting Other Myocardial Fibrosis 1 3 Completed Diagnostic Blood Brain Barrier Defect / CNS Lesion 1 3 Completed Diagnostic Lesion in Body Region 1 3 Recruiting Diagnostic CNS Lesion / Lesion in Body Region 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 485.1 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8114863 No 2012-02-14 2028-09-19 US US10973934 No 2021-04-13 2039-08-06 US US11590246 No 2020-01-17 2040-01-17 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 3.23 mg/mL ALOGPS logP -0.53 ALOGPS logP -11 Chemaxon logS -2.5 ALOGPS pKa (Strongest Acidic) -2.5 Chemaxon pKa (Strongest Basic) 7.51 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 19 Chemaxon Hydrogen Donor Count 9 Chemaxon Polar Surface Area 351.68 Å2 Chemaxon Rotatable Bond Count 24 Chemaxon Refractivity 229.53 m3·mol-1 Chemaxon Polarizability 79.94 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Drug created at November 02, 2022 18:55 / Updated at February 05, 2024 00:28