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At least 19 recordsLinked to original sources
PubMed1987

[Comparative pharmacokinetics and renal accumulation of the iodized contrast media: ioxitalamic acid, ioxaglic acid and iohexol in the rabbit].

Male and female rabbits were given a I.V. bolus injection of a single 5 ml/kg dose of either ioxitalamic acid, ioxaglic acid or iohexol. Animals were killed 2 hours, 8 hours and 24 hours after the injection. One group of animals received a continuous I.V. infusion of contrast agent at a constant rate of 2.5 ml/kg/hour of four hours. Animals were killed 30 minutes after the end of the infusion. Plasma and tissue concentrations of contrast agents were assayed using an HPLC method. A pharmacokinetic study was performed after the I.V. bolus injection. This study shows that: 1) Plasma elimination half-lives were identical in males and in females as well as for all three products. This half life is about 45 minutes. The distribution volume was identical in male and females as well as for all three products and was comprised between 20% and 26% of body weight. 2) For all three contrast agents, the renal cortical concentrations are higher than in the medulla or the papilla at all the observation times. The renal cortical accumulation of contrast agents is persistent in comparison to plasma concentrations. 3) Ionic and lipophilic properties of contrast agents seem to play an important role on the renal accumulation pattern.

Animals↗
PubMed1983

Effects of ioxaglic acid on cardiac functions during coronary arteriography in canines.

The new monoacid dimer ioxaglic acid (P286), The non-ionic metrizamide (Amipaque) and diatrizoate (Renografin 76) were compared regarding their effects on left ventricular pressure, the first derivative of left ventricular pressure, aortic pressures and on ECG changes during left and right coronary angiography in dogs. Ioxaglate was found to affect most of these parameters less than diatrizoate probably due to its lower osmolality. Ioxaglate should be regarded suitable for coronary angiography. However, ioxaglate was found to have greater effects on the cardiac function than the equiosmolar metrizamide. This is probably due to the chemotoxicity of the anion or possibly to the sodium content of the ioxaglic acid solution.

Angiography↗
PubMed1983

[Ioxaglic acid, a contrast medium with low osmolarity in clinical use].

The article reports on the clinical use of sodium and meglumine ioxaglate/Hexabrix, an angiographic contrast medium of low osmolarity. Due to this low osmolarity, favourable experiences were collected in 287 angiographic examinations. Special attention was paid to the question to what extent the contrast medium was responsible for pain, and it was found that Hexabrix definitely causes less pain than the tri-iodated conventional contrast media. During the examination no pain was registered which would have been indicated verbally or by means of movements as involuntary reactions to pain. In arteriography Hexabrix is definitely superior to the conventional contrast media.

Adolescent↗
PubMed1998

Detection of IgE antibody to a radiocontrast medium.

BACKGROUND: Very little is known about the mechanisms underlying adverse reactions to radiocontrast medium. On the basis of the clinical features of the adverse reactions, it has generally been considered that an IgE-dependent mechanism is not involved in these adverse reactions, and only a few studies have demonstrated the presence of IgE antibody to radiocontrast medium in patient sera. METHODS: We assayed for IgE antibody to ioxaglic acid (Hexabrix), a representative radiocontrast medium, in the sera of patients who had developed adverse reactions to ioxaglic acid. A conjugate was prepared by coupling succinyl ioxaglic acid to human serum albumin. Enzyme immunoassay and radioimmunoassay for the detection of IgE antibody to ioxaglic acid in patient sera were constructed by physical adsorption or by covalent coupling of the conjugate on solid supports. RESULTS: When the radioactivity or the absorbance exceeding the mean plus 3 SD for normal healthy subjects was regarded as positive, IgE antibody was detected in the sera of 47.1% of the patients who had a past history of adverse reactions to ioxaglic acid and 16.2% of those who had experienced adverse reactions to ioxaglic acid within 24 h before the blood collection, although the IgE antibody levels were low. On the other hand, IgE antibody to ioxaglic acid was not detected in the sera of patients with no history of adverse reactions to ioxaglic acid. Inhibition experiments revealed the presence of IgE antibody specific to ioxaglic acid in the serum defined as positive for IgE antibody to ioxaglic acid. The presence of IgE antibody to ioxaglic acid did not always correlate with the activation of mast cells due to the occurrence of adverse reactions to ioxaglic acid. CONCLUSIONS: A small amount of IgE antibody to ioxaglic acid was detected in the sera of some patients with a history of adverse reactions to ioxaglic acid, and these adverse reactions may be partly explained by the presence of IgE antibody in the serum of at least some patients.

Antibodies↗
PubMed1992

Effects of new intravascular contrast agents on [Ca2+]i transients and contraction in cultured ventricular myocytes.

We examined the effects of four kinds of intravascular contrast agents (amidtrizoic acid, iohexol, iopamidol, and ioxaglic acid) on [Ca2+]i transients (indo-1 fluorescence) and cell contraction (video motion analyzer), using cultured chick embryo ventricular myocytes. Exposure of ventricular myocytes to amidtrizoic acid (a conventional contrast agent) reduced the [Ca2+]i transients and the sensitivity of the contractile elements to [Ca2+]i. Ioxaglic acid (a low osmotic contrast agent) also reduced the [Ca2+]i transients, but did not significantly change the sensitivity of the contractile elements to [Ca2+]i. Neither iohexol nor iopamidol (nonionic contrast agents) reduced the [Ca2+]i transients, but both significantly decreased the sensitivity of the contractile elements to [Ca2+]i. A marked negative inotropic effect of amidtrizoic acid was caused by both calcium binding and hypertonicity. The less marked depression of contractility produced by ioxaglic acid is possibly the result of calcium binding, but is not caused by hypertonicity. The negative inotropism produced by nonionic contrast agents (iohexol and iopamidol) was due to hypertonicity, but not due to alterations in the [Ca2+]i transients. Exposure of ventricular myocytes to nonionic contrast agents (iohexol and iopamidol) slowed decay in the [Ca2+]i transients with increased end-diastolic [Ca2+]i. After washing out the nonionic contrast agents, these parameters returned to control levels. On the other hand, exposure to amidtrizoic acid decreased end-diastolic [Ca2+]i without changing decay time in the [Ca2+]i transients. After washing out amidtrizoic acid, there was a prolongation of half decay time in [Ca2+]i transients with a significant increase in end-diastolic [Ca2+]i and cell position. Diastolic dysfunction just after washout of amidtrizoic acid was possibly caused by an increase in [Na+]i due to sodium influx during exposure to the contrast agent.

Animals↗
PubMed1996

Human basophil/mast cell releasability. XI. Heterogeneity of the effects of contrast media on mediator release.

BACKGROUND: The activation of basophils and mast cells plays a role in the pathogenesis of anaphylactoid reactions occurring during the administration of iodinated radiocontrast media. METHODS: We compared the effects of three contrast media (CM), Hexabrix (sodium and meglumine salts of ioxaglic acid), Telebrix (sodium and meglumine salts of ioxitalamic acid), and Optiray (ioversol) on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2 and leukotriene C4) mediators from human basophils and mast cells isolated from lung, skin, and heart tissue. The commercial preparations were evaluated in parallel with the pure substances. Mannitol was used as a positive control inducing histamine release (HR) by hyperosmolar stimulation. RESULTS: Hexabrix (0.1 to 0.3 mol/L), Telebrix (0.1 to 0.5 mol/L), Optiray (0.2 to 0.5 mol/L), and the corresponding pure substances concentration-dependently induced HR from basophils. A positive correlation was found between CM osmolality and HR from basophils. Mast cells isolated from different anatomic sites responded differently to the three CM. Hexabrix and Optiray induced histamine and tryptase release from human lung mast cells, but not from human skin mast cells. No correlation was found between the osmolality of CM and HR from human lung mast cells. There was a significant correlation between the percent of histamine and tryptase release induced by CM from human lung mast cells. Hexabrix, Telebrix, and Optiray also induced histamine and tryptase release from human heart mast cells. None of the CM induced the de novo synthesis of leukotriene C4 or prostaglandin D2 from basophils or mast cells. The kinetics of HR caused by CM differed according to the drug used and the cell (basophils or human lung mast cells) examined. CM-induced HR from basophils and human lung mast cells was temperature-dependent, partially influenced by extracellular Ca2+ concentrations, and not modified by preincubation of basophils with IL-2 or IL-3. CONCLUSIONS: These results provide evidence of the heterogeneity of the effects of CM on mediator release from human basophils and mast cells from different anatomic sites. They also suggest that hyperosmolarity may be an important factor in the activation of basophils by CM, but less relevant for mast cells. CM induce only the release of preformed mediators. The measurement of plasma tryptase might be clinically useful for monitoring adverse reactions caused by CM.

Basophils↗
PubMedDate not supplied

Delayed adverse reaction to sodium ioxaglic acid-meglumine.

A patient had a maculopapular rash, fever, hepatic cytolysis, rhabdomyolysis, eosinophilia and raised total IgEs after coronarography with ioxaglic acid-meglumine (Hexabrix). Intradermal test to ioxaglic acid-meglumine was positive 48 hrs later. Histological examination revealed perivascular lymphocytic infiltration, with predominantly CD45Ro+ and CD8+ T cells and apoptotic basal keratinocytes. This case documents a late hypersensitivity reaction to ioxaglic acid-meglumine.

Angioplasty↗
PubMed2003

In vivo comparative antithrombotic effects of ioxaglate and iohexol and interaction with the platelet antiaggregant clopidogrel.

RATIONALE AND OBJECTIVES: Experiments were designed to (1) compare the effects of iodinated contrast media (CM) on a rat model of arterial thrombosis, (2) evaluate which element of the ioxaglate solution supports its antithrombotic activity, and (3) investigate the interaction of ionic and non-ionic CM with the antiplatelet agent clopidogrel. MATERIALS AND METHODS: Carotid thrombosis was induced in rats by extravascular application of a filter paper soaked in FeCl3 (35% vol/wt), proximal to an ultrasonic flow probe. (1) The antithrombotic potential of low-osmolar ionic (ioxaglate Na/meglumine) or nonionic contrast media (iohexol and iodixanol) (all 1600 mg iodine/kg, IV) was assessed by measuring the time to occlusion (TTO) of the carotid artery and the thrombus weight (TW). (2) Isotonic saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), sodium ioxaglate (600 mOsm/kg) and sodium and meglumine ioxaglate (commercial solution) were tested under similar conditions. (3) Interaction with clopidogrel was tested by injecting lower dose of CM (960 mg iodine/kg) 2 hours after clopidogrel (2 mg/kg per os). RESULTS: (1) Ioxaglate prolonged TTO when compared with saline (30.0 +/- 1.1 minute vs. 19.6 +/- 2.4 minutes, P< 0.001), whereas iohexol had no effect (21.3 +/- 1.3 minutes). Ioxaglate's effect was associated with a reduction in TW with ioxaglate versus saline (2.6 +/- 0.4 mg and 4.7 +/- 0.7 mg, respectively, P< 0.05) whereas TW remained unchanged in the iohexol group (4.2 +/- 0.4 mg). The nonionic dimer iodixanol induced a direct vasoconstrictor effect on the carotid artery and was consequently excluded from the study. (2) Neither iso-osmolar nor hyperosmolar solutions of meglumine had any effect on TTO whereas both sodium and meglumine salts of ioxaglic acid prolonged TTO, suggesting that the antithrombotic effect of ioxaglate is mediated by the ioxaglic acid moiety alone as neither meglumine, osmolality or sodium played a significant role. (3) A synergistic effect on TTO was found when ioxaglate was associated with clopidogrel whereas no such effect was observed with iohexol. CONCLUSIONS: These data show a greater in vivo antithrombotic potential for the ionic contrast medium ioxaglate than for the non-ionic contrast medium iohexol and, for the first time, a synergistic effect between a contrast medium and a platelet antiaggregant drug in vivo.

Animals↗
PubMed1994

Effects of contrast media on the stria vascularis.

The effects of contrast media on the stria vascularis were electron microscopically studied in mice after intravenous injection of amidotrizoate, iopamidol or ioxaglic acid at 10 or 20 ml/kg body weight. In furosemide-load groups, contrast media were injected via the tail vein at 10 ml/kg with preadministration of furosemide at 20 mg/kg body weight. In both groups, the stria vascularis was prepared for study 10 min after the injection of contrast media. No morphological changes could be found after administration of 10 ml/kg injection of any of the three contrast media. However, administration of 20 ml/kg of amidotrizoate caused a high degree of intercellular dilatation between marginal and intermediate cells. Iopamidol caused a slight degree of dilatation, and ioxaglic acid caused no change. In the furosemide-load groups, amidotrizoate induced severer effects than iopamidol while ioxaglic acid induced no effect. From these results it was concluded that contrast media affect the stria vascularis parallel with osmolality, although some ionic effect of amidotrizoate should be considered when it is used in combination with furosemide.

Animals↗
PubMed1990

Comparison of toxicity of radiocontrast agents to renal tubule cells in vitro.

We have previously reported that radiocontrast agents induce direct renal tubule cell toxicity in vitro. The observed toxic effects were markedly potentiated by concomitant hypoxia. In addition, we have reported that the ionic radiocontrast agent diatrizoic acid is more toxic than the nonionic radiocontrast agent iopamidol in this system. Using suspensions enriched in rabbit renal proximal tubule segments, we compared the direct toxicities of the ionic dimeric ioxaglic acid to the nonionic monomeric compound iopamidol. Toxicity was assessed by comparing tubule potassium and calcium content, ATP levels, and respiratory rates after exposure to clinically achievable concentrations of radiocontrast agents. Ioxaglate (25 mM) produced significant declines in tubule cation content and respiratory rate with 30 min of hypoxia followed by 60 min of reoxygenation compared to molar-equivalent concentrations of iopamidol under similar conditions. Meglumine, a cationic compound frequently present in ionic contrast agent solutions, and ioxaglate tubule toxicity was additive. Iopamidol and ioxaglate exhibited similar tubule cell toxicity when comparison was based on iodine content. These experimental results suggest that the intrinsic nephrotoxic potential of ioxaglic acid is greater than that of iopamidol on a molar basis, but that the nephrotoxic potential of the two radiocontrast agents is similar when comparison is based upon iodine content.

Adenosine Triphosphate↗
PubMed1983

Two new contrast media in coronary angiography.

Amipaque, ioxaglic acid and Isopaque Coronar 300 were compared in a double blind investigation of coronary angiography in patients with ischemic heart disease. Amipaque affected systolic blood pressure and ECG less than the other contrast media. Ioxaglic acid appeared to give more ST and T changes than Isopaque Coronar.

Adult↗
PubMed1979

A clinical trial of a new low osmolality contrast medium. Sodium and meglumine ioxaglate (Hexabrix) compared with meglumine iothalamate (Conray) for carotid arteriography.

The discomfort of cerebral arteriography is due mainly to the osmolality of the contrast medium injection. A new low osmolality contrast medium--Hexabrix (32% iodine)--sodium and meglumine salts of ioxaglic acid was compared with Conray 280 (28% iodine)--meglumine iothalamate for carotid arteriography in 33 conscious patients. 30 patients preferred the ioxaglate solution which caused significantly less sensation of heat. Three patients could not distinguish between the two media. No patient preferred iothalamate. Ioxaglic acid is a newly synthesized mono-acid dimer. Its salts produce the same osmolality as non-ionics (e.g. metrizamide), and one third of the osmolality of currently used mono-valent salts (e.g. meglumine iothalamate) in solutions of the same iodine content. Low osmolality contrast media have significant clinical advantages and will probably become the media of choice for arteriography and venography.

Adult↗
PubMed1996

Contrast media are incomplete secretagogues acting on human basophils and mast cells isolated from heart and lung, but not skin tissue.

To investigate the mechanisms of anaphylactoid reactions to radiocontrast media, in vitro mediator release induced by three iodinated contrast agents was examined using peripheral blood basophils and mast cells purified from human lung parenchyma, heart, and skin tissues. Three iodinated contrast agents, sodium and meglumine salts of ioxaglic acid, sodium and meglumine salts of ioxithalamic acid, and ioversol, were incubated with basophils purified from peripheral blood and human mast cells isolated and purified from different anatomical sites. Release of preformed (histamine and tryptase) and de novo synthesized mediators (prostaglandin D2 and leukotriene C4) into the supernatans was determined at various contrast medium concentrations after incubation for 60 min. Ioxaglate (0.2-0.3 M), ioxithalamate (0.3-0.5 M), and to a lesser extent ioversol (0.3-0.5 M) induced histamine release from basophils in a concentration-dependent manner. All three induced the release of preformed mediators (histamine and tryptase) from human lung, but not from skin mast cells. They also induced histamine and tryptase release from human heart mast cells. However, they did not induce the de novo synthesis of leukotriene C1 or prostaglandin D2 from human basophils or any type of mast cell examined. Cross-linking of IgE by anti-IgE induced the release of leukotriene C4 or prostaglandin D2 from human basophils or mast cells. Mannitol, an osmotic stimulus, induced the release of histamine from human basophils, but to a lesser extent from mast cells. These results show that different contrast media can differ in their ability to release mediators from enriched preparations of human basophils and mast cells. The three contrast agents examined act on basophils and mast cells as incomplete secretagogues, causing the release of preformed mediators, but not these novo synthesis of chemical mediators. It may be useful to measure plasma tryptase levels to detect adverse reactions caused by iodinated radiographic contrast materials.

Adult↗
PubMed2001

Comparative effects of ionic and nonionic iodinated low-osmolar contrast media on platelet function with the PFA-100 (platelet function analyzer).

RATIONALE AND OBJECTIVES: This study was designed to (1) compare the effects of ionic (ioxaglate) and nonionic (iodixanol and iohexol) iodinated low-osmolar contrast media (CM) on platelet function in human whole blood by using the new PFA-100trade mark, a "platelet function analyzer"; (2) determine the animal species closest to human with regard to platelet reactivity to CM; and (3) evaluate which element of the ioxaglate solution supports this activity. METHODS: For all studies, platelet adhesion and aggregation were measured using the PFA-100trade mark system with adenosine diphosphate-primed collagen membrane cartridges. Results are shown as the membrane closure time (MCT; the longer the MCT, the greater the antiaggregatory effect) and given as medians. Citrated whole-blood samples from six healthy volunteers were mixed for 1 minute with a 10% (vol/vol) solution of ioxaglate, iodixanol, or iohexol or their respective ionic and nonionic controls (isotonic saline and mannitol). The test solution/control solution ratio for the MCT was calculated for the blood of humans, guinea pigs, rabbits, dogs, and rats. Isotonic saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), and sodium ioxaglate (600 mOsm/kg) were tested under similar conditions. RESULTS: All three CM caused significant prolongation of MCT when compared with their respective controls (ioxaglate: 300 seconds, ie, "no closure" on the PFA-100trade mark system; iodixanol: 179 seconds; iohexol: 171 seconds; saline: 115 seconds; mannitol: 118 seconds). The antiplatelet effect of ioxaglate was higher than that of iodixanol and iohexol (P < 0.05). The animal species tested did not differ significantly from the human species with regard to an effect of their blood on MCT. Both ioxaglic acid salts caused a higher prolongation of MCT when compared with saline (sodium salt: 259 seconds; meglumine salt: 212 seconds; P < 0.05 vs. saline) but not versus the ioxaglate commercial solution. Conversely, both iso- and hyperosmolar solutions of meglumine hydrochloride (108 and 128 seconds, respectively) did not lengthen MCT versus saline, but their MCTs were shorter than that of the commercial solution of ioxaglate (P < 0.05). CONCLUSIONS: The ionic CM ioxaglate displayed a greater antiaggregatory effect on human platelets than did both iso-osmolar (iodixanol) and hyperosmolar (iohexol) nonionic CM. This effect seems to be linked to the ioxaglic moiety, because neither osmolality nor sodium or meglumine appeared to play a significant role.

Adult↗