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Different effect of diatrizoate and iopamidol on prostaglandin synthesis in perfused hamster lungs.

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 14C-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 but was not changed by diatrizoate. The amount of radioactivity was decreased in the perfusion effluent and increased in lung lipids by iopamidol. Meglumine diatrizoate increased radioactivity in the effluent with minimal effects on the distribution of radioactivity in lung lipids. Almost all arachidonate metabolites were decreased significantly by iopamidol when compared with hypertonic saline whereas diatrizoate caused an increasing trend in the formation of the metabolites of AA. The present study shows that ionic and nonionic RCM have different effects on the metabolism of arachidonic acid.

Animals↗

Double-blind comparison of iodamide and diatrizoate for excretory urography.

A double-blind comparison of meglumine iodamide and Renografin 60 (52% meglumine diatrizoate and 8% sodium diatrizoate) for bolus excretory urography was performed. Doses of 0.8 cc/kg. to a maximum of 55 cc were administered to fifty patients, twenty-five receiving each drug.There is a suggestion that iodamide may be superior to diatrizoate in pyelocalyceal opacification while being equal to diatrizoate in parenchymal opacification and in types and severity of side-effects.

Adolescent↗

Characteristics of diatrizoate-induced basophil histamine release.

Factors influencing the release of histamine by basophils exposed to the radiocontrast agent diatrizoate were investigated in vitro by use of cells from healthy adult subjects with no history of radiocontrast reactions. Diatrizoate-induced release shared similarities with calcium ionophore-induced release. The response to both agents is dose dependent, enhanced by deuterium oxide, optimal at 37 degrees C, calcium dependent, and enhanced with longer reaction times. Unlike calcium ionophore, however, pretreatment of basophils with diatrizoate may also induce dose-dependent inhibition of reactivity during subsequent challenges with anti-IgE, N-formyl methionine peptide, and calcium ionophore. These findings suggest that diatrizoate may induce histamine release via a calcium ionophore-like mechanism, but other effects on cellular function probably account for its ability to inhibit basophil responsiveness.

Anaphylaxis↗

Biodegradability of the X-ray contrast compound diatrizoic acid, identification of aerobic degradation products and effects against sewage sludge micro-organisms.

Pharmaceuticals and contrast media have been detected in hospital effluents, sewage treatment plants, surface water, and ground water. Only little is known about their elimination during sewage treatment and effects of possible biotransformation products against bacteria. The modified Zahn-Wellens test (ZWT, OECD 302 B) and a test simulating biological sewage treatment (modified OECD 303 A test) were used to assess the biodegradability of the widely used ionic iodinated contrast agent diatrizoic acid (diatrizoate). Effects against sewage sludge bacteria were studied in the two test systems by monitoring the biomarkers quinones, polyamines, phospholipids and adenosine triphosphate. Diatrizoate was biotransformed into 2,4,6-triiodo-3,5-diamino-benzoic acid in the ZWT. 2,4,6-Triiodo-3,5-diamino-benzoic acid was stable under the test conditions of the ZWT. Diatrizoate was not eliminated in the OECD 303 A simulation test. It was not adsorbed by the sewage sludge. No effects of the test compound or its aerobic transformation products against the bacteria present in the sewage sludge were detected using phospholipids, quinones, polyamines, and adenosine triphosphate as biomarkers.

Aerobiosis↗

Assay and purity analysis of diatrizoate sodium in drug product by LC.

An LC procedure was developed to separate diatrizoate sodium from three known impurities. These impurities are 2,4- and 2,6-diiodo-3,5-diacetamidobenzoic acid (DDZA), and the free amine (5-acetamido-3-amino-2,4,6-triiodobenzoic acid). The separation was achieved using a Hamilton, PRP-X100, anion exchange column. The retention of diatrizoate sodium and the impurities was dependent on pH, potassium chloride concentration and phosphate concentration. Increasing any of these mobile phase modifiers decreased the retention time of all of the components. The eluent for assay and purity determination of drug product consisted of 0.1 M potassium chloride and 0.05 M potassium phosphate dibasic in water/acetonitrile (900:100). The mean concentration of diatrizoate sodium in Hypaque Sodium 50% determined over 3 days was 102.3% of label claim with an R.S.D. of 1.3. The accuracy of the purity method, determined by spiking known amounts of the impurities at five concentrations ranging from 0.025 to 0.06% (w/w) into drug product, was 100.1% for DDZA and 94.2% for the free amine. The decomposition of diatrizoate sodium in 0.1 N potassium hydroxide at 85 degrees C followed pseudo first-order kinetics. The calculated half-life was 2 days.

Chemistry, Pharmaceutical↗

A randomized comparison of the nephrotoxicity of iopamidol and diatrizoate in high risk patients undergoing cardiac angiography.

Three hundred seven high risk patients with renal impairment (serum creatinine greater than or equal to 1.5 mg/dl) were randomized in a double-blind manner to either iopamidol (a nonionic, low osmolar radiocontrast agent) or diatrizoate (a conventional radiocontrast agent) at cardiac angiography with subsequent follow-up study of renal function. Baseline clinical and angiographic variables were similar in the iopamidol (n = 155) and diatrizoate (n = 152) groups. Change in renal function after angiography was less pronounced with iopamidol compared with diatrizoate as measured by mean ( +/- SD) increase in 24 h serum creatinine (0.11 +/- 0.2 versus 0.22 +/- 0.26 mg/dl, p less than 0.001), mean maximal increase in serum creatinine (0.2 +/- 0.44 versus 0.38 +/- 0.73 mg/dl, p less than 0.0001) and percent of patients with a maximal increase in serum creatinine greater than 0.5 mg/dl (8% versus 19%, p less than 0.01). Such differences could not be documented in diabetic patients using insulin. There was no significant difference between agents in the number of patients developing clinically severe acute renal dysfunction. It is concluded that iopamidol is less nephrotoxic than diatrizoate in high risk patients at cardiac angiography. However, the difference in nephrotoxicity is small, of no major clinical significance in the majority of high risk patients and could not be documented in insulin-using diabetic patients. Iopamidol may be the preferred agent in certain patients with advanced renal impairment, but further study is warranted.

Acute Kidney Injury↗

Randomized comparison of the cost and effectiveness of iopamidol and diatrizoate as contrast agents for cardiac angiography.

To evaluate the effectiveness and cost of low osmolarity, nonionic contrast agents for cardiac angiography, 443 patients were randomized to receive either iopamidol or diatrizoate. All adverse events that occurred within 24 h of the procedure were recorded prospectively by study personnel and classified according to previously determined criteria. Major events were defined as life threatening or requiring a procedure to treat, or both. Costs of the catheterization procedure, pharmacy, hospital laboratory and treatment of adverse events were determined on the basis of actual resource use. A total of 20 patients (8.5%) had major and 143 (61%) had minor adverse events with diatrizoate use; 10 patients (4.8%) had major and 53 (25%) had minor adverse events with iopamidol (p = 0.12 for major events; p less than 0.001 for total events). Most adverse events were treated fairly easily and inexpensively. The median overall cost was $186 higher for patients after iopamidol use compared with diatrizoate (p less than 0.0001), but all costs except the cost of the contrast agent were not significantly different between the two groups. Thus, patients who received iopamidol for cardiac angiography had a significantly lower rate of adverse events than those who received diatrizoate, but this difference was achieved at a considerably high overall cost.

Angiocardiography↗

[Renal blood flow after selective injection of different dosages of diatrizoate into the renal artery. An experimental study in the dog (author's transl)].

The characteristic biphasic renal haemodynamic response to diatrizoate injected into the renal artery was shown in the dog with the 133-Xenon washout technique. A brief increase in renal blood flow (RBF) during the first ten seconds is followed by a more prolonged period of diminuished RBF. A dose of 4 ml. diatrizoate 60% resulted in the maximum RBF increase of 43% after ten seconds, but even 1 ml. diatrizoate raised the RBF 24%. The initial vasodilator effect of diatrizoate compares well in its extent with the most potent renal vasodilators.

Animals↗

CT-determined canine kidney and urine iodine concentration following intravenous administration of sodium diatrizoate, metrizamide, iopamidol, and sodium ioxaglate.

Following 24-hour fasting and fluid deprivation, sequential changes in CT numbers of the canine kidney were determined in 4 dogs, each of whom received, at intervals, IV sodium diatrizoate, metrizamide, iopamidol, and sodium ioxaglate at a dose of 500 mgI/kg body weight. The urinary bladder was catheterized for baseline determination of urine osmolality and, subsequently, urine volume and CT number, CT number of the bladder urine from 0 to 10 minutes and from 10 to 20 minutes post-injection was obtained by scanning known dilutions of urine in vitro. Peak renal cortical enhancement occurred within 2 minutes of bolus injection and was not dependent on the chemical make-up of the contrast agent. Peak medullary enhancement occurred within 3 minutes of bolus injection. Peak medulla CT number following sodium diatrizoate was significantly less than that following metrizamide (P less than 0.025) or iopamidol (P less than 0.01). Peak medulla CT number was significantly less following sodium diatrizoate (P less than 0.01), metrizamide (P less than 0.01) and iopamidol (P less than 0.05) than following sodium ioxaglate. Urine iodine concentrations followed a similar pattern, with significant differences as follows: sodium diatrizoate less than metrizamide = iopamidol less than sodium ioxaglate. It was concluded that the investigational agents metrizamide, iopamidol, and sodium ioxaglate have theoretical advantage for excretory urography. Differences in renal handling of these agents are detectable, with CT scanning as differences in renal medullary enhancement and urine iodine concentration.

Animals↗

Decreased cerebrospinal fluid production by intravenous sodium diatrizoate.

Intravenous administration of the radiographic contrast agent sodium diatrizoate (50%, 2ml/kg) significantly decreased cerebrospinal fluid (CSF) production in dogs for up to 40 minutes as measured from a lateral ventricular cannula. The magnitude of this decrease exceeded the decrease induced by hypertonic saline. Since hypertonicity could not explain the decrease, an enzymatic mechanism was sought. Choroid plexus carbonic anhydrase (CA) has been implicated in the elaboration of CSF. The assay of CA activity was a colorimetric measure of the hydration of CO2 where reaction time is related to the amount of active CA present. The inhibition of dog red blood cell and choroid plexus CA by sodium diatrizoate was compared with that by the known CA inhibitor acetazolamide. Acetazolamide (48 mM) produced almost complete inhibition whereas the inhibition by sodium diatrizoate (84 mM) was not significantly different from control. These results suggest that neither hypertonicity nor CA inhibition is the cause of the reduced CSF production after intravenous injection of sodium diatrizoate in dogs.

Acetazolamide↗

Pretreatment with steroids before intravenous injection of diatrizoate or iohexol. Effects on urine and serum profiles.

The effects on urine and serum profiles of intravenous injection of diatrizoate, iohexol, or saline were studied in male rats pretreated with steroids or saline. Using urinary albumin, glucose, sodium, and the enzymes lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) as markers of glomerular and tubular function, it was found that diatrizoate caused temporary glomerular and tubular dysfunction; the effect was independent of the kind of pretreatment. Iohexol did not cause increased glomerular permeability in steroid- and saline-pretreated rats. When used following saline, iohexol induced increased excretion of three tubular components, whereas iohexol plus steroids caused increased excretion of all five tubular components. The dysfunctional effect of iohexol plus steroids was less than that of diatrizoate plus steroids. The serum components revealed no abnormalities induced by either contrast media or methylprednisolone. Pretreatment with steroids has no effect on the glomerular or tubular dysfunctional effect of diatrizoate, whereas it worsens the temporary tubular dysfunctional effect of iohexol in rats.

Acetylglucosaminidase↗

Acute side effects of iopromide and diatrizoate in urography.

PURPOSE: In a prospective study, we compared the acute (0-2 h) side effects of ionic and nonionic contrast media in 767 patients undergoing intravenous urography. MATERIAL AND METHODS: A nonionic contrast medium (iopromide) was compared to an ionic contrast medium (diatrizoate). RESULTS: Side effects occurred in 25 patients (7.9%) receiving iopromide and in 104 patients (23.1%) receiving diatrizoate (p < 0.01). The reactions in the iopromide group were mild in 11 patients, moderate in 5, and severe in 1. The reactions were 83, 19 and 2, respectively, in the diatrizoate group. The number of reactions that required treatment was equal in the two groups (p > 0.05). CONCLUSION: At intravenous urography, iopromide induced fewer side effects compared to diatrizoate.

Acute Disease↗

Muscle toxicity of diatrizoate and iohexol in rabbits. A model for local tissue damage.

The potential tissue irritating effect of diatrizoate and iohexol was studied by injecting the contrast media into the right longissimus dorsi muscle of rabbits. The left muscle served as control. The animals were sacrificed 3 days after the injection, at which time muscle tissue was examined for macroscopic changes and loss of the muscle enzyme creatine kinase (CK) from the injection site was determined. An irregular area of necrotic muscle tissue and a hemorrhage was found at the injection site in rabbits given diatrizoate, whereas iohexol only caused hemorrhage. The local loss of CK activity following diatrizoate (0.64 g muscle tissue) was statistically significantly greater than following iohexol (0.18 g muscle tissue). It is concluded that this model seems to be useful for identification of the irritating potential of contrast media. It is also concluded that diatrizoate caused more damage to the local muscle tissue than iohexol.

Animals↗

Low sodium diet, indomethacin, and contrast media. A comparison between renal effects of diatrizoate and iohexol in rats.

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol, or saline in 30 adult Wistar rats, which received a low sodium diet for 14 days, and indomethacin intravenously 2 hours and immediately before contrast medium or saline injection. A control group of 10 rats, which also received low sodium diet, got saline alone and no indomethacin or contrast medium. Diatrizoate increased albuminuria during the first 22 hours after its injection whereas iohexol did not have any significant effect on albuminuria. Both contrast media caused tubular dysfunction, but there was significant difference between them during the first 2 hours after injection. Compared to the effect of saline, iohexol but not diatrizoate caused increased excretion of lactate dehydrogenase and N-acetyl-beta-glucosaminidase for 2 days. Iodine measurements showed delayed excretion of both media. Light microscopy showed focal location of dilated tubular profiles with hydrophia, which were only present in kidneys exposed to contrast media. It is concluded that in rats fed on a low sodium diet administration of indomethacin in relation to iohexol has a greater tubular cell effect than diatrizoate, which in turn has a greater effect on the glomerular permeability. The excretion of both media is delayed.

Animals↗

Nephrotoxicity of cyclosporin A and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxicity.

Acetylglucosaminidase↗

Intravenous injection of ioxilan, iohexol and diatrizoate. Effects on urine profiles in the rat.

Effects of intravenous ioxilan, a new third generation non-ionic contrast medium, diatrizoate, iohexol and saline on urine profiles were compared. Albumin, glucose, sodium, phosphate, and the enzymes NAG, LDH and GGT were followed in 24 normal rats over 7 days. Diatrizoate significantly affected all profile components during the first two hours. Albuminuria was significantly greater after diatrizoate than after iohexol or ioxilan, and excretion of glucose, LDH and GGT was significantly higher than after ioxilan. Both iohexol and ioxilan increased the excretion of albumin, LDH and GGT, while iohexol also significantly increased excretion of glucose and sodium. There was a greater excretion of glucose and GGT after iohexol than after ioxilan. Saline did not induce any changes. At day 7, serum sodium, urea, creatinine, and albumin were normal for all test substances, and kidney histology revealed no difference between the groups of animals. It is thus concluded that both high osmolar ionic and low osmolar non-ionic contrast media may cause temporary glomerular and tubular dysfunction in rats. In this model, the kidney is affected most by diatrizoate, less by iohexol, and least by ioxilan.

Animals↗

Iohexol compared with diatrizoate in pediatric urography.

Iohexol (300 mg I/ml) was compared with meglumine-Na diatrizoate (290 mg I/ml) in a randomized, single blind, parallel investigation in pediatric urography. Urography with iohexol was performed in 25 infants and with diatrizoate in 26. No changes of clinical importance were observed in blood or urine. No patient reactions were observed in the iohexol group, while 3 patients in the diatrizoate group had reactions assessed to be caused by the contrast medium. Iohexol gave somewhat better diagnostic information than diatrizoate.

Adolescent↗

Diatrizoate in computed cranial tomography: a quantitative study.

Plasma diatrizoate concentrations during computed cranial tomography were measured by UV spectrophotometry in 14 patients. A loading dose of 0.82 mg diatrizoate/kg followed by a stead infusion of 0.01 mg/kg was required to attain and maintain plasma concentrations of approximately 400 mg/100 ml. Lowering the beam energy resulted in a substantial increase in the EMI numbers of diatrizoate and significant improvement in the delineation of contrast containing lesions. A contrast index estimating the volume of pixel containing diatrizoate was calculated for five diagnosed lesions and this factor appears to be related to vascularity and extravasation.

Adenocarcinoma↗