(S)-N,N'-Bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxopropyl)amino]-2,4,6-triiodisophthaldiamid

Very soluble in water

Very soluble in methanol. Practically insoluble in chloroform. Miscible with boiling ethanol

Positive

2.35

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

This chemical does not meet GHS hazard criteria for 100% (2 of 2) of all reports.

Not Classified；Reported as not meeting GHS hazard criteria by 2 of 2 companies. For more detailed information, please visit ECHA C&L website.

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory.；Reported as not meeting GHS hazard criteria per 2 of 2 reports by companies.；There are 0 notifications provided by 0 of 2 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

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

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Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.

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As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

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Respiratory Protection: Where respirators are deemed necessary to reduce or control occupational exposures, use NIOSH-approved respiratory protection and have an effective respirator program in place. Gloves: Chemically compatible. For handling solutions, ensure that the glove material is protective against the solvent being used. Use handling practices that minimize direct hand contact. Employees who are sensitive to natural rubber (latex) should use nitrile or other synthetic nonlatex gloves. Use of powdered latex gloves should be avoided due to the risk of latex allergy. Eye Protection: Safety glasses with sideshields are recommended. Face shields or goggles may be required if splash potential exists or if corrosive materials are present. Approved eye protection (e.g., bearing the ANSI Z87 or CSA stamp) is preferred. Maintain eyewash facilities in the work area. Protective clothing: For handling of laboratory scale quantities, a cloth lab coat is recommended. Where significant quantities are handled, work clothing may be necessary to prevent take-home contamination.

Airborne exposure should be controlled primarily by engineering controls such as general dilution ventilation, local exhaust ventilation, or process enclosure. Local exhaust ventilation is generally preferred to general exhaust because it can control the contaminant at its source, preventing dispersion into the work area. An industrial hygiene survey involving air monitoring may be used to determine the effectiveness of engineering controls. Effectiveness of engineering controls intended for use with highly potent materials should be assessed by use of nontoxic surrogate materials. Local exhaust ventilation such as a laboratory fume hood or other vented enclosure is recommended, particularly for grinding, crushing, weighing, or other dust-generating procedures.

To determine if depression of creatinine clearance after administration of contrast medium may be prevented with theophylline. A nonionic, low-osmolality contrast medium (iopamidol) or an ionic, high-osmolality contrast medium (sodium diatrizoate) was administered to 93 patients. Before the examination, these patients were given theophylline or a placebo orally. There were also 30 patients who received an adenosine-uptake inhibitor (dipyridamole). Creatinine clearance and urinary adenosine levels were measured before and after angiography. Creatinine clearance decreased 18% +/- 4 in the placebo-iopamidol group but did not decrease in the theophylline group; urinary adenosine increased 67% +/- 7. Creatinine clearance decreased 42% +/- 5 in the placebo-sodium diatrizoate group and decreased 24% +/- 3 in the theophylline group; urinary adenosine increased 119% +/- 8. In the dipyridamole group in which iopamidol was given, urinary adenosine increased 96% +/- 7 and creatinine clearance decreased 37% +/- 5. Intrarenal adenosine can be implicated in the pathogenesis of hypertonic contrast medium nephrotoxicity.

Complete thrombotic occlusion of the arterial blood flow in the upper extremity was produced after mixture of Isovue 370 (iopamidol) and papaverine hydrochloride during routine angiography. Bolus and then continuous infusion of urokinase failed to dissolve the thrombus. The patient required a surgical thrombectomy and recovered uneventfully. This case report demonstrates that caution should be exercised when Isovue 370 and papaverine are used in angiography.

Intrathecal administration of corticosteroids with iopamidol is contraindicated.[US Natl Inst Health; DailyMed. Current Medication Information for ISOVUE-M (iopamidol) injection, solution

In vitro studies with animal blood showed that many radiopaque contrast agents, including iopamidol, produced a slight depression of plasma coagulation factors including prothrombin time, partial thromboplastin time, and fibrinogen, as well as a slight tendency to cause platelet and/or red blood cell aggregation. Transitory changes may occur in red cell and leucocyte counts, serum calcium, serum creatinine, serum glutamic oxaloacetic transaminase (SGOT), and uric acid in urine; transient albuminuria may occur.

Renal toxicity has been reported in a few patients with liver dysfunction who were given oral cholecystographic agents followed by intravascular contrast agents. Administration of intravascular agents should therefore be postponed in any patient with a known or suspected hepatic or biliary disorder who has recently received a cholecystographic contrast agent.

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

V - Various；V08 - Contrast media；V08A - X-ray contrast media, iodinated；V08AB - Watersoluble, nephrotropic, low osmolar x-ray contrast media；V08AB04 - Iopamidol

QV - Various；QV08 - Contrast media；QV08A - X-ray contrast media, iodinated；QV08AB - Watersoluble, nephrotropic, low osmolar x-ray contrast media；QV08AB04 - Iopamidol

To test the hypothesis that iodinated contrast media may induce an elevation in serum potassium level, /contrast media was administered to rabbits and tested in-vitro according to four protocols./ Protocol A: After intravenous infusion of contrast media into six rabbits, alterations of potassium ion concentrations were measured. Protocol B: Fresh rabbit blood was mixed in vitro with contrast media, and the fluctuations in potassium were monitored over a 30-minute period. Protocol C: Similar to protocol B, except that blood from humans with no reaction to contrast media was used. For protocol A, blood potassium levels increased above baseline levels. The elevations were statistically significant (P < .05). For protocol B, diatrizoate and ioxaglate caused a gradual increase in blood potassium levels, but iopamidol did not. In protocol C, all three contrast media caused statistically significant elevation in potassium levels. The release of potassium was statistically significant at 5 minutes (P < .05 for diatrizoate and ioxaglate, and P < .01 for iopamidol). The mean release rates (+/- standard deviation) by means of linear regression analysis were 0.0190 mmol/min +/- 0.0112 with diatrizoate, 0.0159 mmol/min +/- 0.0057 with iopamidol, and 0.0088 mmol/min +/- 0.0033 with ioxaglate. Iodinated contrast media increase blood potassium levels causing release of potassium into intravascular spaces. This potassium release may play some role in contrast medium-induced adverse reactions.

The synthesis of prostaglandins and other metabolic products of arachidonic acid (AA) was investigated in isolated perfused lungs of hamsters during the infusion of various concentrations of meglumine diatrizoate and iopamidol. Forty nmol of (14)C-AA was infused into the pulmonary circulation with radiographic contrast media (RCM), and prostaglandins, thromboxanes, and metabolites of lipoxygenases were analyzed from the nonrecirculating perfusion effluent. Arachidonate infusion increased the perfusion pressure. This pressor response was decreased by iopamidol ... The amount of radioactivity was decreased in the perfusion effluent and increased in lung lipids by iopamidol. ... Almost all arachidonate metabolites were decreased significantly by iopamidol when compared with hypertonic saline ...

The pharmacokinetics of iopamidol 370 (Iopamiro), a non-ionic water soluble organic iodine compound, were studied in adults with different degrees of chronic renal failure and in healthy volunteers. After 50 mL were administered i.v., plasma and urine levels were determined. The main pharmacokinetic parameters were calculated on the basis of bi-compartmental open model. There were significant differences from healthy volunteers in half-life beta, which increased with the degree of renal failure as the clearance values decreased. Half-life beta was equal to 1.67 h in healthy volunteers, 4.24 h in patients with mild renal failure and 10.03 h in patients with severe renal failure. The clearance decreased as follows: 0.11 (L/h kg) in healthy volunteers, 0.06 (L/h kg) in patients with mild renal failure and 0.02 (L/h kg) in patients with severe renal failure. No significant differences were found in distribution volume values nor in half-life alpha.

The pharmacokinetics of intravenously administered iopamidol in normal subjects conform to an open two-compartment model with first order elimination (a rapid alpha phase for drug distribution and a slow beta phase for drug elimination). The elimination serum or plasma half-life is approximately two hours; the half-life is not dose dependent.

JR13W81H44

IOPAMIDOL

Established Pharmacologic Class [EPC] - Radiographic Contrast Agent

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

Iopamidol is a Radiographic Contrast Agent. The mechanism of action of iopamidol is as a X-Ray Contrast Activity.

IOPAMIDOL

Radiographic contrast media (CM) induce renal vasoconstriction and may initiate induced nephropathy. Endothelin (ET), a vasoconstrictor, and nitric oxide (NO), a vasodilator, which are synthesized in the kidney by the vascular endothelium as well as by tubular epithelial and glomerular mesangial cells, are key modulators of renal circulation after CM administration. Intravascular CM, in addition, induces pronounced diuresis and natriuresis. The aim of the present study was to evaluate and compare changes in endogenous vasoactive mediators and contrast-induced natriuresis after CM administration. Diagnostic angiographic procedures were performed in 14 patients (9 males and 5 females) using the non-ionic CM Iopamidol. Before and immediately after angiography, venous blood and urine samples were obtained. The urinary excretion of ET-1 and nitrates/nitrites (NOx), and the fractional excretion of sodium (FENa) were measured and analyzed. The urinary excretion of both ET-1 and NOx increased significantly (p < 0.05) after angiography, and urinary ET-1 and NOx excretion was correlated with an increase in FENa (p < 0.05). Exposure to CM in humans is associated with an increase in urinary ET and NOx. The excretion of sodium following CM administration is associated with an increase in urinary ET and NOx. ET and NO might be important in the renal change in humans after CM administration.

No iodinated compound other than Iopamidol was found in the urine of subjects who received intrathecal injection of 10 mL of Iopamiro "300". The compound was neither metabolized nor altered in its optical configuration and urinary iodide content was always in the normal range. Between 72 and 85% of injected Iopamidol was excreted within 72 h of injection.

It is not known whether this drug is excreted in human milk.

The pharmacokinetics of iopamidol in both normal and abnormal tissue have been shown to be variable. Contrast enhancement appears to be greatest soon after administration of the contrast medium, and following intraarterial rather than intravenous administration. ...

For more Absorption, Distribution and Excretion (Complete) data for Iopamidol (8 total), please visit the HSDB record page.

MEDICATION

Use (kg) in Switzerland (2009): >2500；Use (kg; approx.) in Germany (2009): >10000；Use (kg; exact) in Germany (2009): 20149；Use (kg) in USA (2002): 102000；Consumption (g per capita) in Switzerland (2009): 0.32；Consumption (g per capita; approx.) in Germany (2009): 0.12；Consumption (g per capita; exact) in Germany (2009): 0.25；Consumption (g per capita) in the USA (2002): 0.36；Excretion rate: 1；Calculated removal (%): 8.8

In the synthesis of iopamidol, reduction of 5-nitroisophthalic acid yields the corresponding amino diacid, which is then iodinated to give 5-amino-2,4,6-triiodoisophthalic acid. Activation of the aromatic nucleus by the amino group is required for the iodination. Treatment of the latter with thionyl chloride results in the dichloride, which is subjected to N-acylation with L-2-acetoxypropionyl chloride (S-configuration) to afford the diacid chloride. Amidation of /the diacid chloride/ with 2-amino-1,3-propanediol (serinol) followed by hydrolysis of the ester group using aqueous sodium hydroxide gives iopamidol.

Preparation: E. Felder, D. Pitre, DE 2547789; eidem, US 4001323 (1976, 1977 both to Savac)