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PubMed1988

Penetration of fleroxacin into prostatic secretion and prostatic adenoma tissue.

In 12 elderly patients, plasma, prostatic secretion and adenoma tissue concentrations of fleroxacin were determined 1-4 h following oral administration of 400 mg. The plasma concentrations ranged between 0.4 and 5.5 micrograms/ml (median 3.7 micrograms/ml), the mean tissue concentrations were slightly higher. The concentrations in prostatic secretion were about one third of the simultaneous plasma concentrations. High concentrations of the concomitantly administered ioxithalamic acid in prostatic secretion are considered as indicative of urinary contamination, and in this case the fleroxacin concentrations are questionable. The drug levels in prostatic adenoma tissue were similar to the concomitantly measured plasma levels.

Administration, Oral↗
PubMed1980

Deiodination kinetics of water-soluble radiopaques.

Deiodination of diatrizoic acid, an anionic radiopaque, was found to be catalyzed by Cu(II). Through a detailed study of o-iodobenzoic acid, a model compound, the copper-catalyzed SN1 mechanism was established based on observations of common ion, salt, and pH effects. Meta- and para-iodobenzoic acids were unreactive. Deiodination thus was facilitated by a neighboring carboxylate that attracted copper. Iopamidol, a nonionic radiopaque, also underwent deiodination. At pH 7 or above, the hydroxide-ion substitution predominated. At pH below 7, the reaction is in favor of the copper-catalyzed SN1 mechanism.

Contrast Media↗
PubMed1978

Complement system activation by contrast media in neuroradiology.

Complement system activation was studied in six series of 12 patients undergoing routine contrast study following IV injection of five recently developed contrast media. The decreasing order of effectiveness on the complement system was as follows: ioxaglic acid, metrizamide, iodamidol. Metrizoic and ioxithalamic acids did not provoke any complement depletion at the doses used in this study. Both pathways of activating the complement system were involved. We could not find any definite correlation with osmolarity, ionic or nonionic formulation, protein binding, or hydrophobicity.

Complement Activation↗
PubMed1985

High-performance liquid chromatography analysis of mezlocillin, piperacillin, their degradation products, and of ioxitalamic acid in plasma and urine of healthy volunteers.

In plasma and urine of 10 healthy volunteers after intravenous administration of 4 g mezlocillin and piperacillin, respectively, the parent compounds as well as degradation products were assayed by high-performance liquid chromatography. Ioxitalamic acid, a renal contrast medium, was administered simultaneously, in order to measure the glomerular filtration rate, and to control the collection of 24-h urine. As metabolite of mezlocillin the corresponding penicilloic acid only was found, whereas in the case of piperacillin a further degradation product was observed. Half of the doses given was recovered in the urine as unchanged drugs, and in addition 5-10% as metabolites. No differences were found in the pharmacokinetic behaviour of both antibiotics.

Adult↗
PubMedDate not supplied

Development, chemistry, and physical properties of iopamidol and its analogues.

A series of 5-hydroxyacylamino-2,4,6-triiodo-N,N'-hydroxy-alkyl-isophtalamides was prepared in order to study the structural requirements for high water solubility and low toxicity. Among the amides substituted by 2-hydroxyethyl; 2,3-dihydroxypropyl; 1,3-dihydroxypropyl-; and 1,1-dihydroxy-methyl-2-oxyethyl- groups, the highest water solubility was obtained with the 1,3-dihydroxypropyl- group. Neither optical resolution of the 2,3-dihydroxypropyl moiety nor amide formation with two different amines improved the water solubility. The optimal solubility was obtained with S-5-alpha-hydroxypropionylamino-2,4,6-triiodoisophtalic acid di-(1,3-dihydroxy-2-propylamide), iopamidol. Iopamidol forms anhydrous and monohydrate crystals, characterized by differential thermal analyses, x-ray diffraction patterns, and solubility patterns. A method for enzymatic assay of the optical purity of iopamidol with lactodehydrogenase is described as well as partition coefficient, ionization constant of the oxyacylamido-group, critical micelle formation, surface tension, and osmolarity.

Angiography↗
PubMed1977

Radiopaque contrast media. XLIV - Preclinical studies with a new nonionic contrast agent.

L-5-alpha-hydroxypropionylamino-2,4,6-triiodoisophthalic acid di-(1,3-dihydroxy-2-propylamide), abbreviated Iopamidol, a new non-ionic water soluble contrast agent for angiography, myelography, ventriculography and for contrast reinforced computer-assisted axial tomography is described. Extensive preclinical testing showed favorable physico-chemical features of the new compound, low systemic toxicity, excellent cardiovascular and renal tolerability, very mild effects on the blood-brain barrier and on nervous tissue.

Animals↗
PubMed1991

[Intestinal contrast imaging in abdominal computed tomography: water or contrast medium?].

The suitability of water as an oral or rectal contrast medium for abdominal CT was studied in 56 patients and compared with an iodine-containing water-soluble contrast medium (ioxital amino acid). In some cases it was impossible to differentiate gastrointestinal structures from extraluminal fluid collections (cystic tumours, ascites, abscesses) and there was poor filling of distal small bowel and colon. The routine use of water can, therefore, not be recommended. In some cases, however, water can result in improved image quality by reducing artifacts and improving the demonstration of the mucosa.

Adolescent↗
PubMed2005

Analysis of iodinated X-ray contrast agents in water samples by ion chromatography and inductively-coupled plasma mass spectrometry.

In this paper, an analytical method for the determination of six iodinated X-ray contrast agents (amidotrizoic acid, iohexol, iomeprol, iopamidol, iopromide, and ioxitalamic acid), iodide, and iodate in water samples is presented. The method is based on a separation of the analytes by ion chromatography (IC) and a subsequent detection by inductively-coupled plasma mass spectrometry (ICP-MS). The method was optimised with respect to separation conditions (column type and eluent composition) and extensively validated. Without pre-concentration of the samples, limits of detection below 0.2 microg/l could be achieved whereby reproducibility was below 6% for all compounds under investigation.

Chromatography, Ion Exchange↗
PubMedDate not supplied

In vitro evaluation of contrast medium concentration and depth effects on the radiographic appearance of specific canine urolith mineral types.

Nine pure mineral types of canine uroliths (bladder or urethral origin only) identified in a chronologic sample from the Minnesota Urolith Center were compared to sequential dilutions of iodinated radiographic contrast medium in vitro. The uroliths studied were those composed of 100% magnesium ammonium phosphate, calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate appatite, calcium hydrogen phosphate dihydrate (brushite), ammonium acid urate, sodium acid urate, cystine, and silica. The radiopacity of the uroliths was classified as radiolucent, isopaque, or radiopaque, as compared to the radiopacity of the contrast medium solutions in which they were placed, using 2.0 mm and 5.0 mm depths in petri dishes radiographed using a table-top technique. A statistically significant relationship was found between the effective atomic number of the uroliths and the effective atomic number of the contrast medium solutions to which they were compared for the endpoints of isopacity, first lucency (in increasing iodine concentration sequence), and optimal visualization of internal architecture. In general, uroliths isopaque or radiolucent in contrast medium solutions weaker than 23.5 mgI2/ml are most likely ammonium acid urate or sodium acid urate. Uroliths isopaque or radiolucent in contrast medium solutions between 23.5 mgI2/ml and 44.4 mgI2/ml are probably magnesium ammonium phosphate, cystine, or silica. Uroliths that remained radiopaque in solutions stronger than 44.4 mgI2/ml, and particularly those radiopaque in contrast medium solutions stronger than 80 mgI2/ml, almost always contained calcium. This relative opacity assessment is proposed for use in double contrast cystography as an aid in differentiating urolith mineral types clinically to facilitate appropriate use of medical protocols to dissolve uroliths or to prevent their growth or recurrence.

Animals↗
PubMed1984

Effect of prostaglandin inhibition on the renal vascular response to ionic and non-ionic contrast media in the dog.

In an attempt to study the role of prostaglandins in the renal vascular response to contrast media in mongrel dogs, renal arterial injections of 6 ml of either the non-ionic contrast medium Iopamidol or the ionic medium diatrizoate meglumine/Na+ were performed, before and after intravenous injection of a buffered solution of acetylsalicylic acid (10 mg/kg) (ASA). Renal blood flow was recorded using non-occluding electromagnetic flow probes. The resting renal blood flow was significantly reduced after ASA. The usual biphasic response to contrast injection was observed both before and after ASA, and using either contrast medium. Analysis of the results failed to show any difference in degree of vasodilation or vasoconstriction after ASA. We conclude that prostaglandins may affect the resting level of renal blood flow but are not mediators of the instantaneous changes in response to contrast injection.

Animals↗
PubMed1977

Pharmacological investigation of cardiovascular and haemodynamic effects of salts of ioxitalamic acid in anaesthetized dogs.

Aqueous solutions of salts of ioxitalamic acid were infected by intravenous, intracarotid, proximal intra-aortic, and intrafemoral route. We observed cardiovascular effects of small magnitude and short duration. They are composed of hypotension (intravenous and intracarotid route), hypotension followed by hypertension (intra-aortic route), changes of LVP, dLVP/dt and contractile strength parallel with those in blood pressure, bradycardia, increased femoral blood flow. Several factors seemed to be involved in the mechanism of these effects: vagal reflex, transient myocardial depression, peripheral vasodilating effect, increased volaemia. By all routes of administration used, the infection of non-iodinated solutions [NaCl, glucose, methylglucamine (MGL) and monoethanolamine (MEA) hydrochloride] of the same osmolarity as ioxitalamate solution, resulted in similar effects.

Animals↗
PubMed1980

The effect of contrast media of low osmolality on the peripheral arterial blood flow in the dog.

The intravascular contrast media in current use are solutions of salts of tri-iodinated substituted benzoic acids. Haemodynamic changes following injection of these contrast media are due mainly to their high osmolar concentration which is five to eight times physiological levels. In this study we compare the effect in dogs on femoral arterial flow following femoral arterial injection of three new low osmolality contrast media (Amipaque, Iopamidol and Hexabrix) compared to conventional contrast media (Coronary 280). Conventional salts such as Conray 280 cause a marked vasodilatation and increase in femoral blood flow to about twice pre-injection levels. The three new low osmolality contrast media cause much less vasodilation and increase in femoral blood flow (+32%). There was no significant difference between the effects of any of the three new media. The experiment suggests that any of three new low osmolality contrast media should be suitable for femoral arteriography as they cause much less vasodilatation (and therefore discomfort) than conventional contrast media. Our results do not indicate a preference for any of the three new contrast agents.

Animals↗
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↗
PubMedDate not supplied

Autoradiographic method for quantitative evaluation of the blood-brain barrier effects of contrast media.

Opening of the blood-brain barrier after intravenous injection of different contrast media has been investigated by a quantitative autoradiographic technique using 14C-aminoisobutyric acid (AIB) as the blood-brain barrier radiotracer. In this study, experiments were carried out in adult rats. Animals were injected intravenously with 2 ml/kg of the tested contrast medium, and immediately afterward with the blood-brain radiotracer AIB. The following contrast media have been tested: diatrizoate 38%, ioxithalamate 38%, ioxaglate 38%, the nonionic product metrizamide 40%, and a new nonionic product P-297, 400 mg l/ml. Control animals were injected intravenously with saline 0.9% (2 ml/kg) before the injection of the tracer. The degree of blood-brain barrier opening was quantitatively assessed by calculating the capillary rate constant for blood-to-brain transfer of AIB (ki) from the brain activity and the arterial integral for a 6 min experiment. Preliminary data seem to indicate that the intravenous injection of 2 ml/kg of a constant medium may produce a tiny opening of the blood-brain barrier. But, if this is so, this blood-brain barrier opening is of a very low magnitude in the normal brain and there are no obvious differences between the test contrast agents injected intravenously.

Animals↗
PubMed1987

Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material.

The x-ray contrast mediums used over the past three decades have been salts of iodinated acids administered in highly hypertonic concentrations. We conducted a multiinstitutional randomized study of the protective effects of pretreatment with corticosteroids against reactions to intravenous contrast material. We gave 6763 patients two doses of oral corticosteroids (methylprednisolone, 32 mg) approximately 12 hours and 2 hours before challenge with contrast material, one dose of oral prednisolone approximately 2 hours before challenge, or placebo in the same dosages. The two-dose corticosteroid regimen, but not the one-dose regimen, significantly reduced the incidence of reactions of all types (P less than 0.05) except a category of reactions dominated by hives, for which the reduction approached significance (P = 0.055). In recent years, several relatively expensive monomeric nonionic iodinated compounds having approximately half the osmolality of the corresponding ionic compounds and a lower reaction rate have become available. With our two-dose corticosteroid regimen, the incidence of reactions necessitating therapy in patients receiving the ionic medium approximated that reported in an unblinded nonrandomized study of patients receiving a newer intravenous nonionic medium without corticosteroid pretreatment. We conclude that the much less expensive ionic medium, if administered with corticosteroid pretreatment, may serve as a reasonable alternative to intravenous nonionic medium, without loss of safety.

Administration, Oral↗
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↗
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↗
PubMed2000

Potential harmful effect of iodinated intravenous contrast medium on the clinical course of mild acute pancreatitis.

HYPOTHESIS: A worse clinical outcome might be expected in patients with acute pancreatitis (AP) who receive intravenous contrast medium for a nondynamic contrast-enhanced computed tomographic (CECT) study early during hospital admission. DESIGN: Cohort analytic study. SETTING: Tertiary care center. PATIENTS: Of 126 patients with mild AP, 52 patients underwent CECT to establish AP diagnosis (group 1), and the remaining 74 did not (group 2). MAIN OUTCOME MEASURES: Survival and development of local or systemic complications during the hospital stay. Potential confounders were demographic, clinical, and biochemical data, as well as therapeutic measures. The Atlanta classification was used to define local and systemic complications. RESULTS: Mean age, etiology of AP, prognostic score on admission, and pharmacologic treatment were similar between groups. Local and systemic complications were more frequently observed in patients who underwent CECT (odds ratio, 11.4; 95% confidence interval, 2.0-64.8; P =.008). Six patients, all in group 1, developed a pancreatic abscess (odds ratio, 20.8; P =.004). In 5 of them, a second CECT showed more severe AP changes. The association between CECT and abscess development was more apparent in patients with a body mass index of 25 or more and/or nasogastric suction. Six patients in group 1 and 1 in group 2 had systemic complications (odds ratio, 9. 5; P =.01). There were no deaths. CONCLUSIONS: The observed increased incidence of local and systemic complications in patients with mild AP who undergo CECT, particularly in those with a body mass index of 25 or more, suggests a potentially harmful effect of intravenous contrast medium. Until this issue is clarified, it seems reasonable to restrict the use of dynamic CECT to patients with severe AP, protracted clinical course, or suspected local septic complication.

Acute Disease↗