 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C24H21I6N5O8 |
| Molecular Weight | 1268.88 |
| Exact Mass | 1268.57 |
| CAS # | 59017-64-0 |
| Related CAS # | 67992-58-9 (mono-hydrochloride salt) |
| PubChem CID | 3742 |
| Appearance | Typically exists as solid at room temperature |
| Density | 2.545g/cm3 |
| Boiling Point | 887.9ºC at 760 mmHg |
| Melting Point | 302°C |
| Flash Point | 490.8ºC |
| Index of Refraction | 1.786 |
| LogP | 4.691 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 43 |
| Complexity | 1090 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | 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 |
| InChi Key | TYYBFXNZMFNZJT-UHFFFAOYSA-N |
| InChi Code | 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) |
| Chemical Name | 3-[[2-[[3-[acetyl(methyl)amino]-2,4,6-triiodo-5-(methylcarbamoyl)benzoyl]amino]acetyl]amino]-5-(2-hydroxyethylcarbamoyl)-2,4,6-triiodobenzoic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vivo | Ioxaglic acid can detect comparable GAG concentrations and is sensitive to the GAG gradient seen in cartilage[2]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Following the intravascular route of injection, Ioxaglic acid is rapidly transported through the circulatory system to the kidneys. The pharmacokinetics of radiopaque contrast media given by the IV route are described by a two-compartment model with a rapid alpha phase for drug distribution and a slow beta phase for the elimination of the drug. Following the intravenous administration of 50 mL of ioxaglic acid in 10 healthy volunteers, the mean peak plasma concentration occurred at two (1-3) minutes, reaching a concentration of 2.1 (1.8-2.8) mg/mL. Approximately 50 percent of the intravenously administered dose was recovered in the urine at two hours, and 90% percent was recovered at the 24 hour time point. Excreted unchanged in the urine The liver and small intestine provide the major alternate route of excretion. In patients with severe renal impairment, the excretion of this contrast medium through the gallbladder and into the small intestine sharply increases. Ioxaglate salts cross the placental barrier in humans and are excreted unchanged in human milk. 245 ml/kg Following intravascular injection, HEXABRIX is rapidly transported through the circulatory system to the kidneys and is excreted unchanged in the urine. The pharmacokinetics of intravascularly administered radiopaque contrast media are usually best described by a two compartment model with a rapid alpha phase for drug distribution and a slower beta phase for drug elimination. Following the intravenous administration of 50 mL of HEXABRIX in 10 normal volunteers, the mean peak plasma concentration occurred at two (1-3) minutes, reaching a concentration of 2.1 (1.8-2.8) mg/mL. Approximately 50 (42-67) percent of the intravenously administered dose was recovered in the urine at two hours, and 90 (68-105) percent was recovered at 24 hours. Following intravenous injection, HEXABRIX is rapidly excreted by the kidneys. HEXABRIX may be visualized in the renal parenchyma one minute following bolus injection. Maximum radiographic density in the calyces and pelves occurs in most instances within 7 to 12 minutes after injection. In patients with severe renal impairment, contrast visualization may be substantially delayed. In brain scanning, contrast media do not accumulate in normal brain tissue due to the blood brain barrier (BBB). The increase in x-ray attenuation usually seen in normal tissue following contrast medium injection is due to the presence of the contrast medium in the blood pool. Disruption in the BBB, such as occurs in malignant tumors of the brain, allows accumulation of contrast medium within the interstitial tumor tissue; adjacent normal brain tissue does not contain the contrast medium. For more Absorption, Distribution and Excretion (Complete) data for Ioxaglate (8 total), please visit the HSDB record page. Metabolism / Metabolites Excreted unchanged. Biological Half-Life Hexabrix 320 is rapidly eliminated by the kidneys with a half-life of about 90 minutes In 10 patients with normal renal function, the alpha and beta half-lives of HEXABRIX were 12 (4-17) and 92 (61-140) minutes, respectively. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Intravenous iodinated contrast media are poorly excreted into breastmilk and poorly absorbed orally so they are not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. Guidelines developed by several professional organizations state that breastfeeding need not be disrupted after a nursing mother receives an iodine-containing contrast medium. However, because there is no published experience with ioxaglate during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Ioxaglic acid binds very weakly to plasma proteins and is quickly eliminated unchanged by the kidneys (glomerular filtration with no re-absorption or tubular secretion). Interactions Intravenous injection of ioxaglate (4 g iodine kg(-1)), an iodinated radiographic contrast medium, caused a marked protein extravasation, pulmonary edema and a decrease in the arterial partial oxygen pressure in rats. All of these reactions to ioxaglate were reversed by the pretreatment with gabexate mesilate (10 and 50 mg kg(-1), 5 min prior to injection) or nafamostat mesilate (3 and 10 mg kg(-1)), in which the inhibition was complete after injection of nafamostat mesilate (10 mg kg(-1)). Both gabexate mesilate and nafamostat mesilate inhibited the activity of purified human lung tryptase, although the latter compound was far more potent than the former. Ioxaglate enhanced the nafamostat-sensitive protease activity in the extracellular fluid of rat peritoneal mast cell suspensions. Tryptase enhanced the permeability of protein through the monolayer of cultured human pulmonary arterial endothelial cells. Ioxaglate, when applied in combination with rat peritoneal mast cells, also produced the endothelial barrier dysfunction. These effects of tryptase and ioxaglate were reversed by nafamostat mesilate. Consistent with these findings, immunofluorescence morphological analysis revealed that tryptase or ioxaglate in combination with mast cells increased actin stress fiber formation while decreasing VE-cadherin immunoreactivity. Both of these actions of tryptase and ioxaglate were reversed by nafamostat mesilate. These findings suggest that tryptase liberated from mast cells plays a crucial role in the ioxaglate-induced pulmonary dysfunction. In this respect, nafamostat mesilate may become a useful agent for the cure or prevention of severe adverse reactions to radiographic contrast media. Renal failure has been reported in patients with liver dysfunction who were given an oral cholecystographic agent followed by an intravascular iodinated radiopaque agent and also in patients with occult renal disease, notably diabetics and hypertensives. In these classes of patients there should be no fluid restriction and every attempt made to maintain normal hydration, prior to contrast medium administration, since dehydration is the single most important factor influencing further renal impairment. Non-Human Toxicity Values LD50 Dog intravenous >10.2 g Iodine/kg LD50 Rabbit intravenous >6.4 g Iodine/kg LD50 Rat intravenous >8.0 g Iodine/kg LD50 Rat intravenous 13,300 mg/kg LD50 Mouse intravenous 11.2 g Iodine/kg |
| References |
[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. |
| Additional Infomation |
Therapeutic Uses Intravascular injection of a radiopaque diagnostic agent opacifies those vessels in the path of the flow of the contrast medium, permitting radiographic visualization of the internal structures of the human body until significant hemodilution occurs. Contrast Media THERAPEUTIC CATEGORY: Diagnostic aid (radiopaque medium) HEXABRIX is indicated for use in pediatric angiocardiography, selective coronary arteriography with or without left ventriculography, peripheral arteriography, aortography, selective visceral arteriography, cerebral angiography, intra-arterial digital subtraction angiography, intravenous digital subtraction angiography, peripheral venography (phlebography), excretory urography, contrast enhancement of computed tomographic head imaging and body imaging, arthrography and hysterosalpingography. /Included in US product label/ For more Therapeutic Uses (Complete) data for Ioxaglate (7 total), please visit the HSDB record page. Drug Warnings /BOXED WARNING/ SEVERE ADVERSE EVENTS - INADVERTENT INTRATHECAL ADMINISTRATION: Serious adverse reactions have been reported due to the inadvertent intrathecal administration of iodinated contrast media that are not indicated for intrathecal use. These serious adverse reactions include: death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. Special attention must be given to insure that this drug product is not administered intrathecally. Ionic iodinated contrast media inhibit blood coagulation, in vitro, more than nonionic contrast media. Nonetheless, it is prudent to avoid prolonged contact of blood with syringes containing ionic contrast media. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimize thromboembolic events. Numerous factors, including length of procedure, catheter and syringe material, underlying disease state and concomitant medications may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended including close attention to guidewire and catheter manipulation, use of manifold systems and/ or three-way stopcocks, frequent catheter flushing with heparinized saline solutions and minimizing the length of the procedure. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting. Serious or fatal reactions have been associated with the administration of iodine containing radiopaque media. It is of utmost importance to be completely prepared to treat any contrast medium reaction. As with any contrast medium, serious neurologic sequelae, including permanent paralysis, can occur following cerebral arteriography, selective spinal arteriography and arteriography of vessels supplying the spinal cord. The injection of a contrast medium should never be made following the administration of vasopressors since they strongly potentiate neurologic effects. In patients with subarachnoid hemorrhage, a rare association between contrast administration and clinical deterioration, including convulsions and death, has been reported. Therefore, administration of intravascular iodinated contrast media in these patients should be undertaken with caution. A definite risk exists in the use of intravascular contrast agents in patients who are known to have multiple myeloma. In such instances anuria has developed resulting in progressive uremia, renal failure and eventually death. Although neither the contrast agent nor dehydration has separately proved to be the cause of anuria in myeloma, it has been speculated that the combination of both may be causative factors. The risk in myelomatous patients is not a contraindication to the procedure; however, partial dehydration in the preparation of these patients for the examination is not recommended since this may predispose to precipitation of myeloma protein in the renal tubules. No form of therapy, including dialysis, has been successful in reversing the effect. Myeloma, which occurs most commonly in persons over 40, should be considered before instituting intravascular administration of contrast agents. For more Drug Warnings (Complete) data for Ioxaglate (29 total), please visit the HSDB record page. Pharmacodynamics This drug allows for the visualization of important organs and structures in the body. It binds to tissues, allowing the blockage of X-rays and diagnostic visualization in various soft tissues and body cavities. The joint spaces in addition to the uterus and fallopian tubes may be visualized by the direct injection of the contrast medium into the region to be studied. |
Solubility Data
| Solubility (In Vitro) | 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 |
| Solubility (In Vivo) |
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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7881 mL | 3.9405 mL | 7.8810 mL | |
| 5 mM | 0.1576 mL | 0.7881 mL | 1.5762 mL | |
| 10 mM | 0.0788 mL | 0.3940 mL | 0.7881 mL |