Ioxaglic acid can detect comparable GAG concentrations and is sensitive to the GAG gradient seen in cartilage[2].

Absorption, Distribution and Excretion
Following intravenous injection, iosagarate rapidly reaches the kidneys via the circulatory system. The pharmacokinetics of intravenously injected radiocontrast agents can be described using a two-compartment model, with rapid α-phase distribution and slow β-phase elimination. In 10 healthy volunteers, after intravenous injection of 50 mL of iosagarate, the mean peak plasma concentration occurred at 2 (1–3) minutes, reaching 2.1 (1.8–2.8) mg/mL. Approximately 50% of the intravenously injected dose is excreted in the urine after 2 hours, and 90% is excreted after 24 hours. It is primarily excreted unchanged in the urine. The liver and small intestine are the main routes of excretion. In patients with severe renal impairment, the amount of this contrast agent excreted into the small intestine via the gallbladder increases dramatically. Iosagarate can cross the placental barrier and is excreted unchanged in human milk. 245 ml/kg Following intravenous injection, HEXABRIX is rapidly transported to the kidneys via the circulatory system and excreted unchanged in the urine. The pharmacokinetics of intravenously administered radiocontrast agents are generally best described using a two-compartment model, which includes a rapid α-phase drug distribution and a slower β-phase drug elimination. In 10 healthy volunteers, after intravenous injection of 50 mL HEXABRIX, the mean peak plasma concentration occurred at 2 (1–3) minutes, reaching 2.1 (1.8–2.8) mg/mL. Approximately 50% (42–67%) of the dose was excreted in the urine within two hours after intravenous injection, and 90% (68–105%) was excreted after 24 hours. Following intravenous injection, HEXABRIX is rapidly excreted by the kidneys. HEXABRIX can be observed in the renal parenchyma one minute after injection. In most cases, the radioactivity density of the renal calyces and pelvis reaches its maximum within 7 to 12 minutes after injection. Imaging may be significantly delayed in patients with severe renal impairment.
In brain scans, contrast agents do not accumulate in normal brain tissue due to the presence of the blood-brain barrier (BBB). The increased X-ray attenuation typically observed in normal tissue after contrast agent injection is due to the presence of the contrast agent in the blood pool. Disruption of the blood-brain barrier, such as in malignant brain tumors, can lead to the accumulation of contrast agents in the tumor interstitial tissue; adjacent normal brain tissue does not contain the contrast agent.
For more complete data on the absorption, distribution, and excretion of iodosagalic acid (8 types), please visit the HSDB record page.

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Metabolism/Metabolites
Excreted unchanged.

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Biological Half-Life
Hexabrix 320 is rapidly cleared by the kidneys with a half-life of approximately 90 minutes.
In 10 patients with normal renal function, the α and β half-lives of HEXABRIX were 12 (4–17) minutes and 92 (61–140) minutes, respectively.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Very little iodine contrast agents administered intravenously are excreted into breast milk, and their oral absorption rate is also very low. Therefore, they are unlikely to enter the infant's bloodstream and will not cause any adverse effects on breastfed infants. Guidelines developed by multiple professional organizations indicate that breastfeeding mothers do not need to interrupt breastfeeding after receiving iodine-containing contrast agents. However, since there is currently no published experience regarding the use of iodosagaric acid during lactation, other medications may be preferred, especially when breastfeeding newborns or premature infants. ◉ Effects on Breastfed Infants
No relevant published information was found as of the revision date. ◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.
Protein Binding

Isodosagaric acid has a weak binding affinity to plasma proteins and is rapidly excreted unchanged by the kidneys (glomerular filtration, no reabsorption or tubular secretion).

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Interactions
Intravenous injection of iosagarate (4 g iodine kg⁻¹, an iodinated radiocontrast agent) caused significant protein extravasation, pulmonary edema, and decreased arterial oxygen partial pressure in rats. All these responses to iosagarate were reversed by pre-injection of gabexate mesylate (10 and 50 mg kg⁻¹, 5 minutes before injection) or nabemustine mesylate (3 and 10 mg kg⁻¹), with complete inhibition following nabemustine mesylate (10 mg kg⁻¹). Both gabexate mesylate and nabemustine mesylate inhibited the activity of purified human lung trypsin, but the latter was significantly more potent. Iosagarate enhanced the activity of nabemustine-sensitive proteases in rat peritoneal mast cell suspensions. Trypsin enhanced protein permeability through a cultured human pulmonary artery endothelial cell monolayer. Combined administration of iosagarate with rat peritoneal mast cells also led to endothelial barrier dysfunction. Nafamostat mesylate reversed these effects of trypsin and iosagarate. Consistent with these findings, immunofluorescence morphological analysis showed that the combined action of trypsin or iosagarate with mast cells increased the formation of actin stress fibers while reducing the immunoreactivity of VE-cadherin. Nafamostat mesylate reversed both of these effects of trypsin and iosagarate. These findings suggest that mast cell-released trypsin plays a key role in iosagarate-induced pulmonary dysfunction. In this regard, nafamostat mesylate may be an effective drug for treating or preventing serious adverse reactions to radioactive contrast agents.
It has been reported that patients with hepatic impairment who received oral cholecystography followed by intravascular iodinated radiopaque contrast agents, as well as patients with occult kidney disease (especially those with diabetes and hypertension), have experienced renal failure. For these patients, fluid intake should not be restricted before contrast agent injection, and every effort should be made to maintain normal hydration, as dehydration is the most important factor leading to further renal impairment.

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Non-human toxicity values
Canine intravenous LD50 >10.2 g iodine/kg
Rabbit intravenous LD50 >6.4 g iodine/kg
Rat intravenous LD50 >8.0 g iodine/kg
Rat intravenous LD50 13,300 mg/kg
Mouse intravenous LD50 11.2 g iodine/kg

[1]. New contrast media in cerebral angiography: animal experiments and preliminary clinical studies. Invest Radiol. Nov-Dec 1980;15(6 Suppl):S270-4.

[2]. Spectral CT imaging of human osteoarthritic cartilage via quantitative assessment of glycosaminoglycan content using multiple contrast agents. APL Bioeng. 2021 Apr 1;5(2):026101.

Therapeutic Uses
Intravascular injection of radiopaque diagnostic agents allows for visualization of blood vessels along the contrast agent's flow path, enabling radiographic imaging of internal structures before significant blood dilution.
Contrast Agents
Therapeutic Category: Diagnostic Aids (Radiopaque Media)
HEXABRIX is indicated for pediatric cardiovascular angiography, selective coronary angiography (with or without left ventricle angiography), peripheral arteriography, aortic angiography, selective visceral arteriography, cerebral angiography, intra-arterial digital subtraction angiography, intravenous digital subtraction angiography, peripheral venography (venography), excretory urography, contrast enhancement for computed tomography head and body imaging, arthrography, and hysterosalpingography. /Included in US Product Labelling/
For more complete data on the therapeutic uses of iodoxazolate (7 types), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Serious Adverse Events - Accidental Intrathecal Injection: Serious adverse reactions have been reported due to accidental intrathecal injection of iodinated contrast agents that are not suitable for intrathecal administration. These serious adverse reactions include: death, seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and cerebral edema. Special care must be taken to ensure that this drug is not administered intrathecally.
In vitro studies have shown that ionic iodinated contrast agents are more effective at inhibiting blood clotting than non-ionic contrast agents. Nevertheless, caution should be exercised to avoid prolonged contact between blood and syringes containing ionic contrast agents. Serious thromboembolic events leading to myocardial infarction and stroke have been reported when using ionic and non-ionic contrast agents in angiography, although these events are rare and can be fatal. Therefore, especially in angiography, precise intravascular drug delivery techniques must be employed to minimize the occurrence of thromboembolic events. Numerous factors, including procedure duration, catheter and syringe materials, underlying medical conditions, and concomitant medications, can contribute to thromboembolic events. For these reasons, meticulous angiography techniques are recommended, including close monitoring of guidewire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent flushing of the catheter with heparinized saline, and minimizing procedure time. Using plastic syringes instead of glass syringes has been reported to reduce, but not completely eliminate, the possibility of extracorporeal coagulation. Serious or fatal reactions have also occurred with iodine-containing contrast agents. Adequate preparation for any contrast agent reaction is crucial. As with any contrast agent, severe neurological sequelae, including permanent paralysis, can occur after cerebral angiography, selective spinal angiography, and spinal cord feeding angiography. Never administer contrast agents after taking vasopressors, as vasopressors significantly enhance neurological effects. A rare association has been reported between contrast agent injection and clinical deterioration (including seizures and death) in patients with subarachnoid hemorrhage. Therefore, intravascular iodine-containing contrast agent injections should be administered with caution in these patients.
It is known that there are clear risks associated with the use of intravascular contrast agents in patients with multiple myeloma. In such cases, anuria has occurred, leading to progressive uremia, renal failure, and ultimately death. While neither contrast agents nor dehydration have been individually proven to be the cause of anuria in patients with multiple myeloma, it is speculated that the combination of the two may be a contributing factor. The risk of anuria is not a contraindication for this examination in patients with multiple myeloma; however, partial dehydration of these patients prior to the examination is not recommended, as this may lead to the precipitation of myeloma proteins in the renal tubules. Currently, there are no treatments (including dialysis) that can reverse this effect. Multiple myeloma is most common in people over 40 years of age, therefore this disease should be considered before intravascular injection of contrast agents.
For more complete data on drug warnings for iodosagaric acid (29 in total), please visit the HSDB record page.

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Pharmacodynamics
This drug can be used to visualize important organs and structures in the body. It binds to tissues, thus blocking X-rays and enabling diagnostic imaging of various soft tissues and body cavities. By injecting contrast agents directly into the area to be examined, the joint spaces, as well as the uterus and fallopian tubes, can be visualized.

C24H21I6N5O8

1268.88

1268.57

59017-64-0

67992-58-9 (mono-hydrochloride salt)

3742

Typically exists as solid at room temperature

2.545g/cm3

887.9ºC at 760 mmHg

302°C

490.8ºC

1.786

4.691

6

8

10

43

1090

0

OCCNC(C1=C(I)C(C(=O)O)=C(I)C(NC(CNC(C2C(I)=C(C(NC)=O)C(I)=C(N(C(=O)C)C)C=2I)=O)=O)=C1I)=O

TYYBFXNZMFNZJT-UHFFFAOYSA-N

InChI=1S/C24H21I6N5O8/c1-7(37)35(3)20-17(29)10(21(39)31-2)13(25)11(18(20)30)23(41)33-6-8(38)34-19-15(27)9(22(40)32-4-5-36)14(26)12(16(19)28)24(42)43/h36H,4-6H2,1-3H3,(H,31,39)(H,32,40)(H,33,41)(H,34,38)(H,42,43)

3-[[2-[[3-[acetyl(methyl)amino]-2,4,6-triiodo-5-(methylcarbamoyl)benzoyl]amino]acetyl]amino]-5-(2-hydroxyethylcarbamoyl)-2,4,6-triiodobenzoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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