Peringatan Keamanan

Gadolinium-based contrast agents (GBCAs) cross the placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive. Because of the potential risks of gadolinium to the fetus, use gadoteridol only if imaging is essential during pregnancy and cannot be delayed.^L49871

In animal reproduction studies in rats, gadoteridol doubled the incidence of post-implantation loss at up to 16 times the recommended human dose (RHD). There were no adverse developmental effects observed in rabbits with intravenous administration of gadoteridol during organogenesis at doses up to 19 times the recommended human dose of 0.1 mmol/kg.^L49871

Clinical consequences of overdose with gadoteridol have not been reported. The safety of gadoteridol has been tested in clinical studies using doses up to 0.3 mmol/kg and no clinical consequences related to increasing dose have been observed to date. Gadoteridol can be removed by hemodialysis.^L49871

No animal studies have been performed to evaluate the carcinogenic potential of gadoteridol.^L49871

No changes in reproductive performance and outcome of pregnancy were caused in rats and rabbits by daily intravenous administration of gadoteridol to parent animals before and during gestation up to 1.5 mmol/kg/day (15 times the recommended human dose).^L49871

Gadoteridol did not demonstrate genotoxic activity in: bacterial reverse mutation assays using Salmonella typhimurium and Escherichia coli; a mouse lymphoma forward mutation assay; an in vitro cytogenetic assay measuring chromosomal aberration frequencies in Chinese hamster ovary cells; and an in vivo mouse micronucleus assay at intravenous doses up to 5.0 mmol/kg.^L49871

Gadoteridol

DB00597

small molecule approved investigational

Deskripsi

Gadoteridol is a macrocyclic nonionic gadolinium that provides contrast enhancement of the brain, spine, and surrounding tissues, resulting in improved visualization (compared with unenhanced MRI) of lesions with abnormal vascularity or those thought to disrupt the normal blood-brain barrier.A263076,A263081,L49871 It was 1 of the 3 macrocyclic gadolinium-based contrast agents (GBCAs) that was mandated by the EMA to replace linear gadolinium-based contrast agents due to concerns about retained gadolinium in the brain.^A263076

Initially approved by the FDA in 1992, gadoteridol received additional approval in 2020 for use in pediatric patients less than 2 years old.^L49876

Struktur Molekul 2D

Berat 558.68

Wujud liquid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) The elimination half-life (mean ± SD) is about 1.57 ± 0.08 hours.[L49871] From population PK model of pediatric subjects receiving a single intravenous dose of 0.1 mmol/kg of gadoteridol, the mean distribution half-life (t<sub>1/2,alpha</sub>) was 0.14 ± 0.04 hours in pediatric subjects 2 years to 6 years of age, 0.18 ± 0.07 hours in pediatric subjects 6 years to 12 years of age, and 0.20 ± 0.07 hours in adolescent subjects older than 12 years of age. The mean elimination half-life (t<sub>1/2,beta</sub>) was 1.32 ± 0.006 hours in pediatric subjects 2 years to 6 years, 1.32 ± 0.07 hours in pediatric subjects 6 years to 12 years of age, and 1.61 ± 0.19 hours in adolescent subjects older than 12 years of age. Pharmacokinetic simulations indicate similar half-life values for gadoteridol in pediatric subjects less than 2 years of age when compared to those reported for adults.[L49871] In patients with impaired renal function, the serum half-life of gadoteridol is prolonged. After intravenous injection of 0.1 mmol/kg, the elimination half-life of gadoteridol was 10.65 ± 0.06 hours in mild to moderately impaired patients (creatinine clearance 30 to 60 mL/min) and 9.10±0.26 hours in severely impaired patients not on dialysis (creatinine clearance 10 to 30 mL/min).[L49871]

Volume Distribusi The plasma distribution volume (mean ± SD) for the non-renally impaired adults was 0.205 ± 0.025 L/kg.Following GBCA administration, gadolinium is present for months or years in the brain, bone, skin, and other organs. [L49871]

Klirens (Clearance) The renal and plasma clearance rates (1.41 ± 0.33 mL/ min/kg and 1.50 ± 0.35 mL/ min/kg, respectively) of gadoteridol are essentially identical, indicating no alteration in elimination kinetics on passage through the kidneys and that the drug is essentially cleared through the kidney.[L49871] The mean serum clearance of gadoteridol in patients with normal renal function was 116.14 ± 26.77 mL/min, compared to 37.2 ± 16.4 mL/min in patients with mild to moderate renal impairment and 16.0 ± 3.0 mL/min in patients with severe renal impairment.[L49871]

Absorpsi

From population PK model of pediatric subjects receiving a single intravenous dose of 0.1 mmol/kg of gadoteridol, the mean C_max was 0.66 ± 0.21 mmol/L in pediatric subjects 2 years to 6 years of age, 0.58 ± 0.06 mmol/L in pediatric subjects 6 years to 12 years of age, and 0.68 ± 0.12 mmol/L in adolescent subjects older than 12 years. The mean AUC_0-? was 0.74 ± 0.20 mmol/L*h in pediatric subjects 2 years to 6 years of age, 0.74 ± 0.09 mmol/L*h in pediatric subjects 6 years to 12 years of age, and 0.98 ± 0.09 mmol/L*h in adolescent subjects older than 12 years of age. Pharmacokinetic simulations indicate similar half-life, AUC, and C_max values for ProHance in pediatric subjects less than 2 years of age when compared to those reported for adults.^L49871

Metabolisme

It is unknown if biotransformation or decomposition of gadoteridol occurs in vivo.^L49871

Rute Eliminasi

Gadoteridol is eliminated in the urine with 94.4 ± 4.8% (mean ± SD) of the dose excreted within 24 hours post-injection. Over 80% of the dose was recovered in urine for pediatric subjects after 10 hours.^L49871 In patients with moderately and severely impaired renal function about 97% and 76% of the administered dose was recovered in the urine within 7 days and 14 days, respectively.^L49871

Interaksi Obat

727 Data

Cyclosporine	Cyclosporine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Icosapent	Icosapent may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefotiam	Cefotiam may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Mesalazine	Mesalazine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefmenoxime	Cefmenoxime may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefmetazole	Cefmetazole may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Pamidronic acid	Pamidronic acid may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Tenofovir disoproxil	Tenofovir disoproxil may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Indomethacin	Indomethacin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cidofovir	Cidofovir may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefpiramide	Cefpiramide may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ceftazidime	Ceftazidime may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Loracarbef	Loracarbef may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefalotin	Cefalotin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Nabumetone	Nabumetone may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ketorolac	Ketorolac may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Tenoxicam	Tenoxicam may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Celecoxib	Celecoxib may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefotaxime	Cefotaxime may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Tolmetin	Tolmetin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Foscarnet	Foscarnet may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Rofecoxib	Rofecoxib may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Piroxicam	Piroxicam may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Methotrexate	Methotrexate may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cephalexin	Cephalexin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Fenoprofen	Fenoprofen may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Valaciclovir	Valaciclovir may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Valdecoxib	Valdecoxib may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Diclofenac	Diclofenac may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Sulindac	Sulindac may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Bacitracin	Bacitracin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Amphotericin B	Amphotericin B may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cephaloglycin	Cephaloglycin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Flurbiprofen	Flurbiprofen may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Adefovir dipivoxil	Adefovir dipivoxil may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Pentamidine	Pentamidine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Etodolac	Etodolac may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Mefenamic acid	Mefenamic acid may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Acyclovir	Acyclovir may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Naproxen	Naproxen may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Sulfasalazine	Sulfasalazine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Phenylbutazone	Phenylbutazone may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Meloxicam	Meloxicam may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Carprofen	Carprofen may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefaclor	Cefaclor may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Diflunisal	Diflunisal may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Tacrolimus	Tacrolimus may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ceforanide	Ceforanide may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Salicylic acid	Salicylic acid may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Meclofenamic acid	Meclofenamic acid may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Acetylsalicylic acid	Acetylsalicylic acid may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Carboplatin	Carboplatin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Oxaprozin	Oxaprozin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ketoprofen	Ketoprofen may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Balsalazide	Balsalazide may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ibuprofen	Ibuprofen may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefditoren	Cefditoren may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Atazanavir	Atazanavir may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Colistimethate	Colistimethate may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefuroxime	Cefuroxime may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefapirin	Cefapirin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefadroxil	Cefadroxil may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefprozil	Cefprozil may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ceftriaxone	Ceftriaxone may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Olsalazine	Olsalazine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Lumiracoxib	Lumiracoxib may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefamandole	Cefamandole may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefazolin	Cefazolin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefonicid	Cefonicid may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefoperazone	Cefoperazone may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefotetan	Cefotetan may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefoxitin	Cefoxitin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ceftizoxime	Ceftizoxime may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefradine	Cefradine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Magnesium salicylate	Magnesium salicylate may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Salsalate	Salsalate may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Choline magnesium trisalicylate	Choline magnesium trisalicylate may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefepime	Cefepime may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefacetrile	Cefacetrile may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ceftibuten	Ceftibuten may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cefpodoxime	Cefpodoxime may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Antrafenine	Antrafenine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Aminophenazone	Aminophenazone may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Antipyrine	Antipyrine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Tiaprofenic acid	Tiaprofenic acid may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Lopinavir	Lopinavir may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Etoricoxib	Etoricoxib may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Hydrolyzed Cephalothin	Hydrolyzed Cephalothin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cephalothin Group	Cephalothin Group may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Oxyphenbutazone	Oxyphenbutazone may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Latamoxef	Latamoxef may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Nimesulide	Nimesulide may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Benoxaprofen	Benoxaprofen may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Metamizole	Metamizole may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Zomepirac	Zomepirac may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ceftobiprole	Ceftobiprole may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Cimicoxib	Cimicoxib may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Ceftaroline fosamil	Ceftaroline fosamil may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Lornoxicam	Lornoxicam may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Gadoteridol which could result in a higher serum level.

Referensi & Sumber

Artikel (PubMed)

PMID: 32603767
Del Poggio A, Anello G, Calloni SF, Vezzulli P, Pereira C, Iadanza A, Falini A, Anzalone N: Diagnostic efficacy and safety of gadoteridol compared to gadobutrol and gadoteric acid in a large sample of CNS MRI studies at 1.5T. J Neuroradiol. 2022 Jan;49(1):73-79. doi: 10.1016/j.neurad.2020.06.005. Epub 2020 Jun 27.
PMID: 25922578
Gutierrez JE, Rosenberg M, Seemann J, Breuer J, Haverstock D, Agris J, Balzer T, Anzalone N: Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study. Magn Reson Insights. 2015 Apr 7;8:1-10. doi: 10.4137/MRI.S19794. eCollection 2015.

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Produk: 4 • International brands: 0

Produk

ProHance

Injection, solution • 279.3 mg/1mL • Intravenous • US • Approved
ProHance

Injection, solution • 279.3 mg/1mL • Intravenous • US • Approved
ProHance

Solution • 279.3 mg / mL • Intravenous • Canada • Approved
ProHance

Liquid • 279.3 mg / mL • Intravenous • Canada • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.