ジアトリゾ酸

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals

3.3

-1.05

WHITE POWDER

Crystals from dilute dimethylformide

Crystals from ethanol (aqueous)

VERY SLIGHTLY SOL IN WATER, ALCOHOL; SOL IN DIMETHYLFORMAMIDE, ALKALI HYDROXIDE SOLUTIONS

In water, 5.0X10+5 mg/L at 25 °C

1.07e-01 g/L

Breast Feeding; Lactation; Milk, Human; Contrast Media; Diagnostic Agents

Diagnostic agents > Radiocontrast media

>250

> 300 °C

179.4 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID0044521]

176.3 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

175.26 Ų [M+H]+

Rhombic needles. Slightly sweet taste; melting point 189-193 °C (decomposition); solubility in water at 20 °C: 89 g/100 mL /Meglumine diatrizoate/

pH between 6.0 & 7.6 /Diatrizoate Meglumine/

SOLN OF DIATRIZOATE SODIUM ARE CONSIDERABLY LESS VISCOUS THAN THOSE PREPD FROM DIATRIZOATE MEGLUMINE /SODIUM DIATRIZOATE/

This chemical does not meet GHS hazard criteria for 10% (1 of 10) of reports.

Danger

H317 (90%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 10 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Benzoic acid, 3,5-bis(acetylamino)-2,4,6-triiodo-

Status: Active Update: 03-12-2019 https://echa.europa.eu/registration-dossier/-/registered-dossier/11883

Diatrizoic acid: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl diatrizoate meglumine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Diatrizoate meglumine/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl diatrizoate sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Diatrizoate sodium/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Diatrizoate meglumine is included on this list. /Diatrizoate meglumine/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Diatrizoate sodium is included on this list. /Diatrizoate sodium/

For more FDA Requirements (Complete) data for DIATRIZOATE (6 total), please visit the HSDB record page.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Neurologic effects, including paraplegia, of diatrizoates may increase during aortography when diatrizoates are administered after hypertensive agents used to increase contrast; this increase is due to contraction of vessels in the splanchic circulation, which forces more of the contrast material into the vessels leading to the spine and spinal cord.

Incidence of delayed (more than 1 hour after administration) reactions (eg. hypersensitivity, fever, skin rash, flu-like symptoms, joint pain, flushing, pruritus, emesis, hypotension, dizziness) to intravenous contrast media may be increased in patients who have received interleukin-2; some symptoms may resemble a "recall" reaction to interleukin-2; supportive medical treatment may be necessary if symptoms are significant; there is some evidence that incidence is reduced if contrast media administration is delayed until 6 weeks after interleukin-2 administration.

Concurrent use /of chymopapain/ with diatrizoates may increase the risk of toxicity, especially if either agent enters the subarachnoid space; it is strongly recommended that diskography not be performed as part of the chemonucleolysis procedure.

Concurrent intravascular administration of diatrizoates with beta-adrenergic blocking agents may increase the risk of moderate to severe anaphylactoid reaction; also, hypotensive effects may be exacerbated; discontinuation of the beta-adrenergic blocking agent may be advisable before administration of contrast media in patients with other risk factors.

For more Interactions (Complete) data for DIATRIZOATE (9 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that diatrizoate is expected to have very high mobility in soil(SRC). The estimated pKa of diatrizoate is 1.13(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Diatrizoate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.6X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Iodinated X-ray contrast agents are considered nondegradable by microorganisms(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that diatrizoate is not expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 1.13(3) indicates diatrizoate will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water or moist soil surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of 1.37(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Iodinated X-ray contrast agents are considered nondegradable by microorganisms(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diatrizoate, which has an estimated vapor pressure of 3.8X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase diatrizoate may be removed from the air by wet or dry deposition(SRC). Diatrizoate does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Diatrizoate was found in outflow from a municipal sewage treatment plant in Germany monitored from 1996-1998; the average concentration was 0.08 ug/L with a maximum of 8.7 ug/L reported; the 90th percentile concentration was 1.5 ug/L, and 22 of 25 samples were above the detection limit of 0.010 ug/L(1). The compound was detected at a concentration of 4 ug/L in surface water treatment employing bank filtration(2). Diatrizoate was detected at a concentration range of approximately 210 to 1.0X10+6 ng/L in an industrial waste water of the Netherlands in 2002. Total riverine discharge was estimated at 8.989 tons/yr in 2002(3). The average concentration of diatrizoate in six sewage treatment works in the United Kingdom sampled in 2001 was 42.1 ng/L; detection limit = 24.0 ng/L(4).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of diatrizoate can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that diatrizoate is expected to have very high mobility in soil. Iodinated diagnostic contrast agents such as diatrizoate leach readily into groundwater(3). The estimated pKa of diatrizoate is 1.13(4), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

/SIGNS AND SYMPTOMS/ Anaphylactic reactions: Anaphylactic reactions, including fatalities, have been reported with the use of Gastrografin. Patients at increased risk include those with a history of a previous reaction to a contrast medium, patients with a known sensitivity to iodine, and patients with a known clinical hypersensitivity (bronchial asthma, hay fever, and food allergies). Medical personnel trained in the treatment of anaphylactic reactions and the necessary drugs and medical equipment should always be readily available when Gastrografin is used.

/SIGNS AND SYMPTOMS/ Neurologic effects, including paraplegia, of diatrizoates may increase during aortography when diatrizoates are administered after hypertensive agents used to increase contrast; this increase is due to contraction of vessels in the splanchic circulation, which forces more of the contrast material into the vessels leading to the spine and spinal cord.

/SIGNS AND SYMPTOMS/ Other adverse effects of intravascular diatrizoate meglumine and diatrizoate sodium include nasal and conjunctival symptoms (e.g., rhinitis, lacrimation, sneezing), urticaria, pruritus, rash, angioedema, edema, weakness, pallor, cramps, sweating, severe retching and choking, and metallic taste. Neutropenia, erythrocyte sludging and agglutination, crenation, and transient changes in coagulation may occur; rarely disseminated intravascular coagulation resulting in death has been reported. Infrequently, immediate or delayed chills can occur, sometimes with fever. Salivary gland swelling may occur a few hours to 4 days after administration of the medium and persist several days.

/SIGNS AND SYMPTOMS/ Arteriography of arterial trunks providing blood supply to spinal-artery branches or selective spinal arteriography can cause mild to severe muscle spasm; severe neurologic reactions including permanent paralysis, paraplegia, and quadriplegia have occasionally been reported

For more Human Toxicity Excerpts (Complete) data for DIATRIZOATE (18 total), please visit the HSDB record page.

AEROBIC: Iodinated X-ray contrast agents are considered nondegradable by microorganisms(1,2). However when incubated with 1mM diatrizoate at 30 °C for 32 days, the fungus Trametes versicolor, has been shown to partially diiodinate C-14 ring-labeled diatrizoate, liberating traces of 14-CO2(1). The three main metabolites identified were 3,5-di(acetamido)-2,6-diiodobenzoic acid, 3,5-di(acetamido)-2,4-diiodobenzoic acid, and 3,5-di(acetamido)-2-iodobenzoic acid(1).

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

diatrizoate

DILI Negative

Intravenous

DOI:10.1016/j.drudis.2019.09.022

An estimated BCF of 3 was calculated in fish for diatrizoate(SRC), using an estimated log Kow of 1.37(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The estimated pKa of diatrizoate is 1.13(1), indicating that this compound will primarily exist as an anion in the aqueous environment and anions do not volatilize from water or moist soil surfaces. Diatrizoate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.6X10-15 mm Hg(SRC), determined from a fragment constant method(2).

/LABORATORY ANIMALS: Acute Exposure/ Hemodynamic changes and contrast nephropathy are well known complications of contrast media injection. However, the mechanisms of toxicity leading to these complications remain unclear. /It was/ hypothesized that contrast media toxicity would manifest as a change in antioxidant enzyme activity, thus leading to tissue damage.This study investigated the effects of injection of ionic high-osmolar diatrizoate, ionic low-osmolar ioxaglate, and nonionic low-osmolar iopromide on the activities of two antioxidant enzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), in the heart and kidney tissue of normal male Wistar rats (n = 51) and streptozotocin (STZ)-induced diabetic rats (n = 54). Activities of GPX and SOD were assayed spectrophotometrically. Renal GPX activities were significantly decreased in both normal (458.3 +/- 64.6 to 385.5 +/- 63.4 mU/mg, p = 0.005) and diabetic rats (669.0 +/- 98.1 vs. 564.0 +/- 153.3 mU/mg, p = 0.035) at 1 hour after diatrizoate injection. Renal SOD activities were not affected after contrast injection. Ioxaglate and iopromide injection did not cause any change in renal antioxidant enzyme activity. In contrast to kidney tissue, there was no significant change in GPX and SOD activities in heart tissue at 1 hour after injection of different contrast media. Intravenous injection of ionic high-osmolar diatrizoate reduced renal GPX activity during the first hour in both normal and STZ-induced diabetic rats. Heart tissue was not prone to antioxidant enzyme activity changes after intravenous contrast media injection. GPX activity reduction can be an important mechanism of nephrotoxicity after contrast media injection.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The biological effects of iodinated contrast media were examined by using spermatogenesis in mouse testis as the experimental model. Spermhead survival and abnormality assays were used as the biological end points. Diatrizoate meglumine/diatrizoate sodium and iopamidol were administered intravenously at equal rates and concentrations. Testicular uptake and clearance of these contrast agents were examined by high-performance liquid chromatography techniques. Appropriate mannitol solutions were employed as osmolality controls. Intravenous administration of the contrast agent or its respective mannitol control resulted in approximately a 30% decrease in spermhead count. A dose-related experiment with mannitol demonstrated that the spermhead count decreased rapidly until 600 mOsm/kg was reached, beyond which this decrease was minimal. Clearance of both contrast media was complete in approximately 4 hours. No significant increase in the induction of spermhead abnormalities was observed. Osmotic substances, such as iodinated contrast agents, affect the process of spermatogenesis.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ No teratogenic effects attributable to diatrizoate meglumine or diatrizoate sodium have been observed in teratology studies performed in animals.

/LABORATORY ANIMALS: Neurotoxicity/ The neurotoxicity of Iohexol was evaluated and compared with the neurotoxicity of sodium diatrizoate. Direct neurotoxicity was evaluated with in vitro rat hippocampal slices, and angiographic neurotoxicity was studied in a cat's spinal cord following thoracic aortography. Sodium diatrizoate caused early excitatory changes in electrical activity and later inhibition in the experiments with the rat brain slices while the cat's spinal cord experiments showed an increase in the ventral root reflexes.

For more Non-Human Toxicity Excerpts (Complete) data for DIATRIZOATE (8 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl diatrizoate meglumine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Diatrizoate meglumine/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl diatrizoate sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Diatrizoate sodium/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Diatrizoate meglumine is included on this list. /Diatrizoate meglumine/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Diatrizoate sodium is included on this list. /Diatrizoate sodium/

For more FDA Requirements (Complete) data for DIATRIZOATE (6 total), please visit the HSDB record page.

V - Various

QV - Various

V08AA01

Diatrizoate is the most commonly used water-soluble, iodinated, radiopaque x-ray contrast medium. Radiopaque agents are drugs used to help diagnose certain medical problems. They contain iodine, which blocks x-rays. Depending on how the radiopaque agent is given, it localizes or builds up in certain areas of the body. The resulting high level of iodine allows the x-rays to make a "picture" of the area. The areas of the body in which the radiopaque agent localizes will appear white on the x-ray film. This creates the needed distinction, or contrast, between one organ and other tissues. The contrast will help the doctor see any special conditions that may exist in that organ or part of the body.

Diatrizoate is an iodine-containing X-ray contrast agent. Iodated contrast agents were among the first contrast agents developed. Iodine is known to be particular electron-dense and to effectively scatter or stop X-rays. A good contrast agent requires a high density of electron-dense atoms. Therefore, the more iodine, the more "dense" the x-ray effect. Iodine based contrast media are water soluble and harmless to the body. These contrast agents are sold as clear colorless water solutions, the concentration is usually expressed as mg I/ml. Modern iodinated contrast agents can be used almost anywhere in the body. Most often they are used intravenously, but for various purposes they can also be used intraarterially, intrathecally (the spine) and intraabdominally - just about any body cavity or potential space.

Radiocontrast medium induced nephrotoxicity is a major clinical problem. There is considerable interest in reducing the incidence of acute renal failure due to the use of radiocontrast media (RCM). Reduction of renal blood flow and direct toxic effect on renal tubular epithelial cells have been postulated as major causes of RCM nephropathy. Understanding the molecular mechanisms by which RCM cause cell damage may allow the development of pharmacological therapy to prevent their nephrotoxicity. In this work we have investigated the signaling pathways that may be affected by RCM. The incubation of human renal tubular proximal cells with sodium diatrizoate, iopromide and iomeprol caused a marked dephosphorylation of the kinase Akt on Ser473 within 5min of incubation. RCM also caused a decrease in cell viability, which was substantially alleviated by transfecting the cells with a constitutively active form of Akt. Further downstream targets of Akt, including the Forkhead family of transcription factors FKHR and FKHRL1, were also dephosphorylated by RCM at Thr24 and Thr32, respectively. The P70S6 kinase was also dephosphorylated at Thr389 and Ser371 by RCM. However there was a more dramatic decrease in phosphorylation of the phosphorylated form of mammalian target of rapamycin (mTOR) and of the extracellular-signal regulated kinases (ERK) 1/2 caused by sodium diatrizoate than by iopromide. These results demonstrate the effect of RCM on some intracellular signaling pathways that may allow understanding of the mechanism of their toxicity and may allow the development of strategies to overcome their adverse effects.

Following rapid IV injection of diatrizoate sodium in patients with normal renal function, blood drug concentrations peak immediately, fall rapidly within 5-10 minutes, and then decline with a halflife of about 30-60 minutes. In patients with severely impaired renal function, the blood drug halflife is reported to be 20-140 hours.

The metabolic behavior of 3-amino-5-acetamido-2,4,6-triiodobenzoate and 3,5-diamino-2,4,6 -triiodobenzoate was examined. Drug retention in rabbits was monitored with a gamma camera. Diatrizoate was partially deacetylated by liver microsomes to 3-amino-5-acetamido-2,4,6-triiodobenzoate and 3,4-diamino-2,4,6-triiodobenzoate. The rabbit converted some of 3,5-diamino-2,4,6-trioodobenzoate to a urinary metabolite which was similar to that formed by liver microsomes.

5UVC90J1LK

DIATRIZOIC ACID

Established Pharmacologic Class [EPC] - Radiographic Contrast Agent

Mechanisms of Action [MoA] - X-Ray Contrast Activity

Diatrizoic acid is a Radiographic Contrast Agent. The mechanism of action of diatrizoic acid is as a X-Ray Contrast Activity.

However, it is not metabolized but excreted unchanged in the urine, each diatrizoate molecule remaining "obligated" to its sodium moiety. The liver and small intestine provide the major alternate route of excretion for diatrizoate. Injectable radiopaque diagnostic agents are excreted unchanged in human milk. Saliva is a minor secretory pathway for injectable radiopaque diagnostic agents.

Diatrizoate meglumine is excreted in breast milk following intravascular administration.

Diatrizoate sodium is very poorly absorbed from the GI tract. In some patients, especially infants and patients with engorgement of the intestinal mucosa, small amounts of the drug may be absorbed from the GI tract and occasionally produce partial visualization of the urinary tract. Following intravesical instillation of diatrizoate sodium, only small amounts of the drug are absorbed into blood through the bladder. Some absorption of diatrizoate sodium into blood may also occur through serous membranes such as the peritoneum or pleura. The drug is rapidly absorbed after IM or subcutaneous injection.

Diatrizoate sodium is rapidly distributed throughout extracellular fluid following intravascular administration. Less than 5% of the drug appears to be bound to plasma proteins.

Diatrizoates, when administered intravenously, cross the placenta and are evenly distributed in fetal tissues. Intra-amniotic injection of diatrizoates has been reported to suppress the fetal thyroid gland.

For more Absorption, Distribution and Excretion (Complete) data for DIATRIZOATE (7 total), please visit the HSDB record page.

Density gradient reagent for blood cell separation. /Sodium diatrizoate/

MEDICATION

MEDICATION (VET)

Use (kg) in Switzerland (2009): >25

(1975) No Data

(1977) No Data

(1975) No Data

(1977) No Data

(1975) GREATER THAN 1.82X10+6 G (SALTS ONLY)

(1977) GREATER THAN 9.08X10+5 G (SALTS ONLY)

Derived from benzoic acid by (1) nitration to the 3,5-dinitro acid, (2) reduction by means of stannous chloride or other reducing agent to the corresponding diamino acid, (3) iodination with iodine monochloride in acetic acid to the 2,4,6-triiodo derivative, or (4) acetylation of the amino groups by use of acetic anhydride.

Diatrizoic acid is reacted with equimolar quantity of NaOH, usually in water for injection to produce soln of required concn. /Sodium diatrizoate/

Diatrizoic acid is reacted with an equimolar quantity of methylglucamine (meglumine), usually in water for injection, to produce a solution of the required concentration. /Diatrizoate meglumine/

66% (660 mg per mL) of diatrizoate meglumine and 10% (100 mg per mL) of diatrizoate sodium with 36.7% (367 mg per mL) of iodine (Rx) /Tradename:/ Gastrografin; MD-Gastroview. /Diatrizoates/

GRADE: USP (as solution for injection) /Sodium diatrizoate/

Information available in 2005 indicated that Meglumine diatrizoate was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Luxembourg, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States, Yugoslavia (1,2) /Meglumine diatrizoate/

Information available in 2005 indicated that Sodium diatrizoate was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Luxembourg, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States, Yugoslavia (1,2) /Meglumine diatrizoate/

Information available in 2005 indicated that Lysine diatrizoate was used in the manufacture of pharmaceutical preparations in the following countries: Austria, Germany, Hungary (1,2)

Information available in 2005 indicated that Calcium diatrizoate was used in the manufacture of pharmaceutical preparations in the following countries: Brazil, Spain (1,2)