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PubMedDate not supplied

Renal and non-renal clearances of iothalamate.

An evaluation of the literature indicated that certain aspects of the disposition kinetics of iothalamate, important to the accurate determination of glomerular filtration rate in dogs and humans, remain to be resolved. The simultaneous clearances of iothalamate and inulin in 5 dogs were determined at three steady-state iothalamate plasma levels (2, 10, and 40 micrograms ml-1) following various rates of intravenous infusion. The iothalamate clearances, both renal and non-renal, were concentration-independent. The overall mean non-renal clearance was 18 per cent (ranging from 9 to 25 per cent) of its plasma clearance. The mean iothalamate/inulin renal clearance ratio was about 0.84 with individual values ranging from 0.72 to 0.95. The significant (4-26 per cent) plasma protein binding of iothalamate in these dogs was the main reason for the lower-than-unity clearance ratios obtained. The literature indicates the existence of up to 25 per cent of non-renal elimination in humans with normal renal function; this is comparable to the present results obtained with dogs but contrary to the assumption, sometimes reported in the literature that non-renal elimination is essentially absent in humans. Binding of iothalamate to plasma proteins from humans was not found in the present study. The above results suggest that for accurate glomerular filtration rate determination in humans and dogs, especially for those with renal impairment, renal clearance rather than plasma clearance should be used, and in the case of dogs it should also be corrected for plasma protein binding. Iothalamate in plasma and urine was analysed by a simple, micro high-performance liquid chromatographic method with UV detection.

Animals↗
PubMed1983

Selective coronary arteriography: a clinical comparison of two contrast agents.

The radiopacity and complications of meglumine iothalamate 52% and sodium iothalamate 26% (Vascoray) were compared with those of meglumine diatrizoate 66% and sodium diatrizoate 10% (Renografin -76) in 2258 patients with and without cardiac disease. There was no difference in radiopacity and the type and incidence of adverse reactions were similar, but the frequency was significantly higher (p less than 0.05) with Vascoray in patients with constrictive pericarditis, dissecting aortic aneurysm, and primary pulmonary hypertension. The difference in the frequency of hypotension, sinus bradycardia, and transient asystole in the Renografin -76 and Vascoray groups was statistically significant. Ventricular arrhythmias occurred in 6% of the patients with primary myocardial disease compared to an average of 0.7% in those without this cardiac abnormality (p less than 0.01), but there was no significant difference in the frequency in the two contrast agent groups. All reactions were treated and the studies were performed without mortality. Results of this study show that iothalamate formulation with sodium to meglumine ratio of 1:2 containing 410 mEq/L of sodium (Vascoray) is suitable and safe for clinical use for roentgenographic studies of the heart, and coronary artery circulation.

Adult↗
PubMed1988

Pharmacokinetics of iothalamate in endstage renal disease.

Some nephrologists make alterations in routine peritoneal and hemodialysis schedules after diagnostic studies that use radiographic contrast agents. A study to determine the pharmacokinetics of one contrast agent, iothalamate, is reported. The plasma (total body) clearance of iothalamate was measured in seven patients who had endstage renal disease (ESRD) and who received maintenance hemodialysis. During an interdialytic period, plasma clearance of iothalamate varied from 0.7 to 5.2 mL/min (3.1 +/- 1.8 mL/min, mean +/- SD) with an elimination rate constant (beta) of 0.0164 +/- 0.01 hr-1, a terminal half-life of 61 +/- 42 hours, and an estimated distribution volume of 11 +/- 3.9 L. Hemodialysis clearance of iothalamate was 104 +/- 54 mL/min. With the assumption that iothalamate is mainly distributed in the extracellular fluid (ECF) compartment, the theoretical fluid shift from the intracellular fluid (ICF) compartment to the ECF compartment was 323 mL after administration of the largest dose (2.1 mL/kg or 1.6 mmol/kg of body weight) of 60% meglumine iothalamate solution. The average maximum serum osmolarity change was less than expected, suggesting some type of internal buffering of meglumine iothalamate. In the first few hours after radiocontrast administration in four patients, the average change in serum osmolarity was 5 mmol/L; the average change in serum sodium concentration during this same time was a decrease of 0.5 mmol/L. The minor increase in ECF volume induced by hyperosmolar contrast agents does not require immediate dialysis in most patients. When needed, however, for contrast-related adverse effects, hemodialysis is efficient in rapidly removing iothalamate.

Aged↗
PubMed2001

Changes in intrarenal oxygenation as evaluated by BOLD MRI in a rat kidney model for radiocontrast nephropathy.

The pathogenesis of radiocontrast nephropathy is poorly understood. In an animal model, inhibition of the synthesis of nitric oxide and prostaglandins appears to predispose rats to severe renal injury following the administration of radiocontrast. Here we have investigated whether administration of radiocontrast, as well as changes in renal medullary oxygenation following pharmacologic inhibition of nitric oxide and prostaglandin synthesis, might be evaluated by blood oxygenation level-dependent (BOLD) MRI. Nineteen anesthetized (Inactin 100 mg/kg) rats were studied. BOLD MRI measurements were performed following administration of L-NAME (N-nitro-L-arginine methyl ester, 10 mg/kg), Indomethacin (10 mg/kg), and a radiocontrast agent (sodium iothalamate 60%, 6 mL/kg). Marked sequential changes in medullary R(*)(2), presumably reflecting decline in medullary pO(2), were noted after each of the pharmacological interventions employed. These results, obtained by noninvasive MRI, are consistent with prior direct recordings of pO(2) and doppler flow in the rat renal medulla after administration of L-NAME, Indomethacin and iothalamate. Medullary oxygenation in rats was reduced by inhibition of the synthesis of prostaglandins and nitric oxide, as well as by intravenous injection of radiocontrast agents. BOLD MRI can noninvasively evaluate changes in medullary oxygenation in rats that appear to predispose acute renal failure. J. Magn. Reson. Imaging 2001;13:744-747.

Animals↗
PubMed1984

Radiopaque liposomes: effect of formulation conditions on encapsulation efficiency.

Liposomes containing sodium ioxitalamate were prepared by sonication. Suitable amounts of purified soybean phosphatidylcholine and cholesterol were used at various molar ratios. Stearylamine or dicetylphosphate were added to this lipid composition when charged liposomes were required. After sonication and removal of unencapsulated solute, this manufacturing process yielded small multilamellar vesicles as confirmed by electron microscopy. These liposomes did not exhibit a narrow range of size distribution; the mean particle size varied from 135 to 145 nm. With respect to the efficiency of encapsulation, two parameters were distinguishable: the volume of encapsulated aqueous space per unit of lipid weight and the percentage of the contrast agent added that became encapsulated in the liposomes. Investigation of the preparative parameters revealed that increased molar ratios of cholesterol yielded higher aqueous volume and iodine contents in the liposomes, which were attributed to a reduction of the liposome permeability to the contrast agent. However, the inclusion of cholesterol into the bilayer liposomal membrane was limited, probably by solubility restrictions. Negatively and positively charged liposomes had higher rates of encapsulation than did neutral liposomes. This result was expected since efficient encapsulation of polar compounds requires formation of large aqueous spaces within the vesicles per mole of lipids. Increase of the lipid fractions at a constant, reduced the aqueous volume entrapped per millimole of lipid and, consequently, the iodine content in the liposomes. However, an increase in the initial sodium ioxitalamate concentration diminished the aqueous volume entrapped in the liposomes but increased the iodine content.

Chemistry, Pharmaceutical↗
PubMed2004

Salutary effects of radiopaque contrast media on the survival of random-pattern skin flaps in the rat: an experimental study.

The radiopaque contrast medium diatrizoate, has a vasodilator effect so that it is used in sudden-deafness secondary ischemic injury. However, ischemic problems are encountered, especially when longer flaps are elevated. A longer flap also has ischemic and relatively ischemic tissue, and may obtain some benefit from contrast media. Forty male Sprague-Dawley rats, weighing about 350-400 g, were used, and randomly divided into four groups (n = 10 rats each group): group 1 was the control, group 2 the diatrizoate, group 3 the iopamidol, and group 4 the iothalamate group. A rectangular 3 x 10 cm caudally based dorsal skin flap was elevated, and sutured back to its original place. In the control group, no pharmacologic agent was administered. Sodium-meglumine-diatrizoate 10 mg/kg/day was administered parenterally in the first experimental group (diatrizoate group); iopamidol 10 mg/kg/day in the second experimental group (iopamidol group); and iothalamate sodium 10 mg/kg/day in the third experimental group (iothalamate group) for 7 postoperative days. On postoperative day 7, all flaps were photographed, and the area of flap survival was measured by using a polar planimeter. The results were statistically evaluated with the Kruskal-Wallis test and Mann-Whitney U-test (P = 0.05). The mean flap survival ranged from 79% in the iopamidol group to 83% in the diatrizoate group, and was significantly greater in all experimental groups (P < 0.05) compared to the control group (59%). There was no significant difference between experimental groups (P < 0.05). We believe that radiopaque contrast media have a beneficial effect in improving skin flap viability when distal flap necrosis is a potential complication of longer flaps.

Animals↗
PubMedDate not supplied

Undifferentiated embryonal sarcoma of the liver treated with chemotherapy: CT imaging in four patients.

BACKGROUND: The purpose of this study was to describe the computed tomography (CT) findings of undifferentiated embryonal sarcoma after chemotherapy and to correlate the CT imaging findings with pathologic findings. METHODS: Ten CT images obtained before and after chemotherapy in four patients with hepatic undifferentiated embryonal sarcoma were retrospectively reviewed and correlated with pathologic findings. RESULTS: After chemotherapy, tumor volume decreased by 50-90% and initially nonresectable tumor or gross residual tumor was successfully excised in three patients. In all patients, enhancing peripheral solid portions and septations changed to low-attenuation areas, and in three patients increased or de novo calcifications were found at the periphery of the tumor. Resected pathologic specimen after chemotherapy showed well-encapsulated masses with central necrosis, fibrosis, and dystrophic calcifications. CONCLUSIONS: These CT findings will be useful in monitoring the treatment response of hepatic undifferentiated embryonal sarcoma during chemotherapy.

Adult↗
PubMed1996

Determination of glomerular filtration rate with Visipaque in patients with severely reduced renal function.

Iodixanol (Visipaque, Nycomed Imaging AS, Oslo, Norway), and isotonic, dimeric and non-ionic contrast medium (CM), and iohexol (Omnipaque, Nycomed Imaging AS, Oslo, Norway), a low-osmolar, monomeric and non-ionic contrast medium, were used as glomerular filtration rate (GFR) markers in patients with severely impaired renal function. Different methods for determining GFR were compared. A total of 16 patients with s-creatinine > 400 mumol/l were enrolled in the study; 8 in each CM group. Serum-iodine was measured, and plasma CM clearance was determined using the Bröchner-Mortensen method, the single-sample method and conventional method. The ratios between the results obtained from the conventional method and each of the two other methods were calculated. These data were plotted against the mean of the pairs compared, and the upper and lower limits of agreement were calculated as the mean ratio +/- 2SD. The comparison showed a high degree of agreement between methods, and the two simpler methods seem to be good alternatives to the conventional method, which gave good estimates of GFR (vs that determined by means of renal 125I-iothalamate clearance) when 24-h blood samples were included. However, slight overestimations of GFR, due to extrarenal excretion of the CM, were observed. In summary, serum clearance of iodixanol, as determined by the Bröchner-Mortensen method or single-sample method seems to be a simple and accurate marker for GFR in patients with severely reduced renal function. The findings obtained with iodixanol were similar to those obtained with iohexol.

Adult↗
PubMed1978

113mIn-DTPA, a useful compound for the determination of glomerular filtration rate (GFR). The binding of 113mIn to DTPA and a comparison between GFR estimated with 113mIn-DTPA and 125I-iothalamate.

For measurement of glomerular filtration rate the usefulness of diethyl traimino penta acic (DTPA) labelled with 113mIndium has been explored. The labelling procedure is very simple, since eluate from an 113mIn generator can be used directly for labelling DTP. The in vitro and in vivo binding of 113mIn to DTPA in competition with serum proteins was studied by gel-filtration. The radioactivity with the 113mIn-DTPA peak represented 100.6, 107.1 and 99.6% of the amount of radioactivity applied to the gel column for the in vivo studies, and 102.0 and 101.4% for the in vitro studies. Futhermore, the clearance of 113mIn-DTPA was compared to the clearance of 125I-iothalamate using the constant infusion technique. The clearance values were found to be nearly equal (r=0.996). It is concluded that 113mIn is almost entirely bound to DTPA after intravenous injection of the 113mIn-DTPA complex, and that the complex is a suitable agent for determination of glomerular filtration rate.

Adult↗