Absorption, Distribution and Excretion
Gadoxate disodium is primarily excreted via the kidneys and hepatobiliary pathway. In healthy volunteers aged 22–39 years, the mean terminal elimination half-life of gadoxate disodium (0.01–0.1 mmol/kg) was observed to be 0.91–0.95 hours. Clearance appears to decrease slightly with age. Pharmacokinetics are dose-linear up to 0.4 mL/kg (0.1 mmol/kg, four times the recommended dose). Following intravenous administration, the plasma concentration-time curve for gadoxate disodium exhibits a biexponential decrease. At steady state, the total volume of distribution of gadoxate disodium is approximately 0.21 L/kg (extracellular fluid); plasma protein binding is less than 10%. Gadoxate disodium cannot cross the intact blood-brain barrier but can diffuse across the placental barrier.
In lactating rats, administration of 0.1 mmol/kg [153Gd] gadoxetate disodium resulted in less than 0.5% of the total radioactivity being transferred to newborn pups via breast milk, with most of this transfer occurring within 2 hours.
Metabolism/Metabolites
Gadoxetate disodium is not metabolized.
Biological Half-Life
In healthy volunteers aged 22–39 years, the mean terminal elimination half-life of gadoxetate disodium (0.01–0.1 mmol/kg) was observed to be 0.91–0.95 hours.

Toxicity Summary
Product Introduction: Gadoxate disodium is a gadolinium-based contrast agent for intravenous administration for use in T1-weighted magnetic resonance imaging (MRI) of the liver to detect and characterize lesions in adult patients with known or suspected focal liver disease. Human Exposure and Toxicity: The most common (≥0.5%) adverse reactions associated with EOVIST use included nausea, headache, fever, dizziness, and back pain. Patients with liver disease underwent gadoxate disodium-enhanced liver MRI. Adverse events (AEs) and their potential association with the drug were documented and assessed. Subgroup analyses were performed on patients with specific medical histories. Spontaneous adverse events and adverse drug reactions (ADRs) were analyzed globally during post-marketing safety surveillance. A total of 1989 patients were enrolled in the clinical development program. A total of 1581/1989 (79.5%) patients received the finally approved dose of 0.025 mmol/kg body weight. Adverse events (AEs) were reported in 10.1% of patients, of which 4.1% were classified as related adverse events. Nausea and headache were the most common related adverse events, each with an incidence of 1.1%. Age, history of contrast agent allergy, cirrhosis, or hepatic or renal impairment did not significantly affect the frequency or type of adverse events. The post-marketing safety surveillance database covers more than 2.2 million patients. Nausea was the most common adverse reaction (ADR), with a reporting rate of 0.00652%; all other symptoms had reporting rates below 0.004%. Gadoxetate disodium has a good safety profile for use on liver MRI. Transient severe respiratory motion artifacts associated with gadoxetate disodium were significantly more common after administration of 20 mL (2 mL/s) and occurred significantly more frequently in patients with chronic obstructive pulmonary disease. This dose-related effect suggests that the mechanism is not an allergic reaction. Animal studies: In dogs, a dose-dependent prolongation of the QTc interval was observed after a single administration of EOVIST, which returned to normal 30 minutes after administration. QTc interval prolongation was observed at doses equal to or greater than 0.1 mmol/kg (equivalent to 2.2 times the human dose). At doses up to 0.5 mmol/kg (equivalent to 11 times the human dose), the maximum QTcF interval prolongation did not exceed 20 ms. Animal reproductive and developmental toxicity studies have been conducted in rats and rabbits. During organogenesis, no teratogenicity was observed with intravenous administration of gadoxetate disodium at doses up to 32 times the recommended single human dose (mmol/m²). However, an increased preimplantation embryo loss rate was observed at doses reaching 3.2 times the recommended single human dose (mmol/m²). Compared to the untreated control group, pregnant rabbits receiving gadoxetate disodium at doses 26 times the recommended single human dose (mmol/m²) experienced increased postimplantation embryo loss and resorption rates, and reduced litter size. However, no maternal toxicity was observed. Due to repeated daily administration of EOVIST to pregnant animals, the total exposure was significantly higher than that of a standard single human dose.

---

Interactions
An interaction study in healthy subjects showed that concomitant administration of the OATP inhibitor erythromycin did not affect the efficacy and pharmacokinetics of EOVIST. No further clinical interaction studies with other drugs were conducted.
Patients with liver disease underwent gadoxetate disodium-enhanced liver magnetic resonance imaging (MRI). Adverse events (AEs) were recorded and their potential association with the drug was assessed. Subgroup analyses were performed for patients with specific medical histories. Spontaneous adverse events and adverse drug reactions (ADRs) were analyzed globally during post-marketing safety surveillance. A total of 1989 patients were enrolled in the clinical development program. Of these, 1581 (79.5%) received the finally approved dose of 0.025 mmol/kg body weight. Adverse events were reported in 10.1% of patients, of which 4.1% were classified as related adverse events. Nausea and headache were the most common related adverse events, each with an incidence of 1.1%. Age, history of contrast agent allergy, cirrhosis, or hepatic or renal impairment did not significantly affect the frequency and type of adverse events. The post-marketing safety monitoring database covers more than 2.2 million patients. Nausea was the most common adverse reaction, with a reporting rate of 0.00652%; the reporting rates for all other symptoms were less than 0.004%. Gadoxetate disodium for liver MRI has an excellent safety profile.

[1]. Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system. Radiology. 1992 Apr;183(1):59-64.

[2]. Estimation of liver function using T1 mapping on Gd-EOB-DTPA-enhanced magnetic resonance imaging. Invest Radiol. 2011 Apr;46(4):277-83.

[3]. Gd-EOB-DTPA enhanced MRI for hepatocellular carcinoma: quantitative evaluation of tumor enhancement in hepatobiliary phase. Magn Reson Med Sci. 2005;4(1):1-9.

[4]. Use of gadoxetate disodium in patients with chronic liver disease and its implications for liver imaging reporting and data system (LI-RADS). J Magn Reson Imaging. 2019 May;49(5):1236-1252.

[5]. Troubleshooting Arterial-Phase MR Images of Gadoxetate Disodium-Enhanced Liver. Korean J Radiol. 2015 Nov-Dec;16(6):1207-15.

[6]. Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium. Heliyon. 2024 Mar 8;10(6):e27419.

Disodium gadoxetate is a paramagnetic contrast agent composed of a disodium salt of gadolinium ions chelated with the lipophilic group ethoxybenzyl (EOB) and bound to diethylenetriaminepentaacetic acid (DTPA). When placed in a magnetic field, gadolinium generates a large magnetic moment, thus creating a large local magnetic field, which can enhance the relaxation rate of nearby protons; therefore, the signal intensity of tissue images observed on magnetic resonance imaging (MRI) may be enhanced. Because this contrast agent is preferentially taken up by normal hepatocytes, MRI can enhance normal liver tissue while tumor tissue is not enhanced. Furthermore, because this contrast agent is excreted in bile, it can be used on magnetic resonance imaging (MRI) to visualize the biliary system.
See also: Disodium gadoxetate (note moved to).

---

Therapeutic Use
EOVIST injection is a gadolinium-based contrast agent for intravenous administration for T1-weighted magnetic resonance imaging (MRI) of the liver to detect and characterize lesions in adult patients with known or suspected focal liver disease.

---

Drug Warning
/Black Box Warning/ Warning: Gadolinium-based contrast agents (GBCAs) increase the risk of NSF in patients with impaired drug clearance. GBCAs should be avoided in these patients unless diagnostic information is critical and cannot be obtained via non-contrast MRI or other means. The risk of NSF is highest in patients with chronic severe kidney disease (glomerular filtration rate <30 mL/min/1.73 m²) or acute kidney injury. Patients should be screened for acute kidney injury and other conditions that may impair kidney function. For patients at risk of chronic kidney decline (e.g., age >60 years, hypertension, or diabetes), glomerular filtration rate (GFR) should be estimated by laboratory tests.
Rarely, anaphylactic and hypersensitivity reactions with cardiovascular, respiratory, and skin manifestations have occurred after EOVIST administration, ranging in severity from mild to severe, including shock. Before administering EOVIST, all patients should be evaluated for a history of contrast agent allergy, bronchial asthma, and/or allergic diseases. These patients may have an increased risk of hypersensitivity to EOVIST; in these clinical situations, the benefits and risks of EOVIST MRI should be carefully weighed. EOVIST should only be used if trained personnel and treatment protocols (including those trained in resuscitation) are readily available to treat hypersensitivity reactions. Most EOVIST hypersensitivity reactions occur within half an hour of administration. Delayed reactions (from several hours to several days) may also occur. Patients should be closely monitored for signs and symptoms of hypersensitivity reactions during and after EOVIST administration. These reactions should be treated with standard medications for treating hypersensitivity reactions.
False high or false low values may occur when serum iron is measured using chelation therapy (e.g., ferrous chelation therapy) for up to 24 hours after EOVIST administration.
Severe renal or hepatic failure may affect the imaging performance of EOVIST. In patients with end-stage renal failure, liver contrast is significantly reduced, attributed to elevated serum ferritin levels. Decreased liver contrast has also been observed in patients with abnormally elevated serum bilirubin (>3 mg/dL). If these patients are using EOVIST, MRI imaging should be performed within 60 minutes of EOVIST administration, using paired sets of non-contrast and contrast-enhanced MRI images for diagnosis. For more complete data on drug warnings for gadoxetate disodium (6 of 6), please visit the HSDB record page.

C23H33N3O11.GD.2[NA+]

730.751220000001

726.076

135326-22-6

770677-60-6;135326-22-6 (sodium);

91754427

White to off-white solid powder

0

14

4

40

746

0

CCOC1=CC=C(C=C1)CC(CN(CCN(CC(=O)[O-])CC(=O)[O-])CC(=O)[O-])N(CC(=O)[O-])CC(=O)[O-].[Gd+3].[Na+].[Na+]

SLYTULCOCGSBBJ-UHFFFAOYSA-I

InChI=1S/C23H33N3O11.Gd.2Na/c1-2-37-18-5-3-16(4-6-18)9-17(26(14-22(33)34)15-23(35)36)10-24(11-19(27)28)7-8-25(12-20(29)30)13-21(31)32;;;/h3-6,17H,2,7-15H2,1H3,(H,27,28)(H,29,30)(H,31,32)(H,33,34)(H,35,36);;;/q;+3;2*+1/p-5

disodium;2-[[2-[bis(carboxylatomethyl)amino]-3-(4-ethoxyphenyl)propyl]-[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate;gadolinium(3+)

Gd EOB DTPA ZK 139834 ZK139834 GdEOBDTPA ZK-139834Gd-EOB-DTPA

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 100 mg/mL (~137.80 mM)
DMSO : ~24 mg/mL (~33.07 mM)

Solubility in Formulation 1: ≥ 2.4 mg/mL (3.31 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 24.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.4 mg/mL (3.31 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 24.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.4 mg/mL (3.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 24.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)