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Effects on erythrocyte aggregation and blood coagulation from iohexol solutions with and without sodium chloride. An in vitro study on the role of ion concentration and osmolality.

Solutions of the nonionic monomeric contrast medium iohexol (300 mg I/ml) with and without added NaCl were investigated for effects on red blood cell aggregation and blood coagulation. Three volumes of a test solution were mixed in test tubes with one volume of human blood. During 30 min samples of the mixture were taken for investigation. Six test solutions were used: 1) iohexol, 2) iohexol+glucose 280 mM, 3) iohexol+NaCl 150 mM, 4) glucose 280 mM, 5) glucose 140 mM+NaCl 75 mM, 6) NaCl 150 mM. Test solutions with NaCl caused no aggregation. Test solutions without NaCl always caused macroscopic red cell aggregates. These aggregates always disappeared when saline was added to the sample. The macroscopic red cell aggregates could be dispersed to microscopic aggregates by shaking the test tubes. During the next 30 min macroscopic aggregates returned in the glucose solution but not in the iohexol solutions. In 30 min, blood mixed with iohexol solutions never coagulated while blood layered on top of the same iohexol solutions always coagulated. Blood mixed with solutions 5 and 6, both without iohexol, always coagulated. It is concluded that adding 150 mM NaCl to iohexol did not eliminate its ability to anticoagulate whole blood, but inhibited its ability to aggregate red cells. This inhibition was not caused by the osmotic effects of the added NaCl.

Blood Coagulation↗

The effect of intrathecal iohexol on visual evoked response latency: a comparison including incidence of headache with iopamidol and metrizamide in myeloradiculography.

Fifty consecutive unselected patients referred for myeloradiculography and examined by the same radiologist, when facilities for measuring the visual evoked response were available, are considered. The effect on the visual evoked response of the examination and the incidence of headache following the use of iohexol as the contrast medium are compared with those after the use of iopamidol and metrizamide reported in a previous study. A total of 400 cases examined with iopamidol and 200 cases examined with iohexol are reviewed with regard to the incidence of headache. Whereas iopamidol and, to a greater extent metrizamide, were found to cause significant lengthening of the visual evoked response latency 20 hours after the radiological examination, iohexol did not. Furthermore there was no significant difference in the 20 hour reading following the use of iohexol compared with the original control group of patients who underwent lumbar puncture alone. There was a lower incidence and severity of headache following the use of iohexol than with iopamidol and a markedly reduced incidence compared with metrizamide. Iohexol is considered less neurotoxic than iopamidol which had previously superceded metrizamide as the contrast medium used for myeloradiculography in the Royal Surrey County Hospital. Volumes of up to 14 ml of iohexol 300 mg I/ml have been used for lumbar radiculography and for total myelography and up to 10 ml for direct lateral cervical puncture. In 350 cases examined to date with iohexol the only serious sequel was a case of chemical meningitis following the lumbar injection of 10 ml of the 300 mg I/ml solution for a cervical examination. The patient made an uneventful recovery.

Clinical Trials as Topic↗

Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques.

RATIONALE AND OBJECTIVES: We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. METHODS: After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. RESULTS: Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to the true GFR. For iohexol, the median overestimation of the GFR was higher with ClAUC-slope when early plasma samples (30-120 min) after injection of the marker were used (5.5 ml.min-1.10 kg-1) than when late samples (180-270 min) were used (4.0 ml.min-1.10 kg-1). After subtracting the median extrarenal clearances of iohexol and 51Cr-EDTA (previously determined in nephrectomized pigs) from their plasma clearances (ClAUC-3comp), the median overestimation of the true GFR was reduced from 2.0 to 1.1 ml.min-1.10 kg-1 with iohexol and from 2.1 to 1.3 ml.min-1.10 kg-1 with 51Cr-EDTA. CONCLUSION: GFR determination with plasma clearance techniques can be improved in three- and one-compartment models by taking late plasma samples and by subtracting the extrarenal plasma clearance of the species. One-compartment models can be improved by determining a correction formula in the species for the early parts of the decay curve of the plasma concentration of the marker.

Animals↗

GFR measurement with iohexol and 51Cr-EDTA. A comparison of the two favoured GFR markers in Europe.

BACKGROUND: The aim of the present study was to compare the most commonly used GFR markers for clearance measurements, 51Cr-EDTA and iohexol, using two different methods for iohexol analysis, HPLC and X-ray fluorescence, referring both to the multiple-sample and single-sample calculations, using 51Cr-EDTA as the reference method. METHODS: Forty-nine patients with an estimated GFR >40 ml/min were included. 51Cr-EDTA and iohexol were injected simultaneously and blood samples were taken 150, 195 and 240 min after injection of the respective marker. RESULTS: The multiple-point clearances, determined from HPLC and X-ray fluorescence, compared to 51Cr-EDTA correlated highly (r=0.92 and 0.95 respectively). The results from single-point clearance comparison, iohexol measured by HPLC vs 51Cr-EDTA, yielded a correlation of r=0.91, while single-point clearance from iohexol, analysed by X-ray fluorescence, obtained a correlation of 0.93 and an intercept statistically different from origo. CONCLUSIONS: Iohexol and 51Cr-EDTA are comparable as GFR markers for multiple-point clearance measurements. The single-sample method for GFR >40 ml/min can be used with a high accuracy. The precision and accuracy of X-ray fluorescence analysis of low concentrations of iohexol were less than those of HPLC. Care should therefore be taken when using X-ray fluorescence that the injected dose of iohexol should result in a plasma concentration level of iodine of at least 0.06 mg/ml at the time of blood sampling.

Adult↗

Calcium antagonistic effects of an angiographic contrast medium in vitro. A comparison of the effects of iohexol with the effects of nifedipine in isolated arteries.

RATIONALE AND OBJECTIVES: Vasodilatation is a well-known side effect of contrast media. Contrast media inhibit the action of vasoconstrictors. The nonionic contrast medium, iohexol, inhibits vasoactive substances to a lesser extent than ionic contrast media. Iohexol inhibited the action of vasoconstrictors in a way that raised suspicion of a calcium antagonistic effect of the medium. The authors test this hypothesis by comparing the inhibitory effect of iohexol with the inhibitory effect of a calcium antagonist (nifedipine). The vasoconstrictors were KCl, which depends on potential-operated calcium channels, and histamine, endothelin-1, and prostaglandin F2 alpha (PGF2 alpha), which depend on receptor-operated calcium channels. METHODS: Segments of rabbit coronary arteries were mounted between two L-shaped prongs in tissue baths containing calcium-free buffer, calcium-free buffer with 10(-8) M nifedipine, or iohexol. One of the vasoconstrictors, KCl, histamine, endothelin-1, or PGF2 alpha, was added to induce a level of activation. Thereafter, increasing concentrations of CaCl2 were added in a stepwise manner, and the contractile responses of the vessel segments were recorded. RESULTS: Addition of CaCl2 caused concentration-dependent vasoconstrictions in the buffer. The effect of adding CaCl2 was inhibited in the buffer with nifedipine and in iohexol when the vessels were activated with histamine, endothelin-1, or PGF2 alpha. When the vessels were activated with the potential-operated calcium channel-dependent vasoconstrictor, KCl, the effect of adding CaCl2 was inhibited in the buffer with nifedipine but not in iohexol. CONCLUSIONS: In vitro, iohexol had the same effect as the calcium antagonist nifedipine on the action of receptor-operated calcium channel-dependent vasoconstrictors. This suggests a calcium antagonistic effect of iohexol on the action of the ROC.

Animals↗

Comparative toxic effects of iobitridol and iohexol on the kidney.

RATIONALE AND OBJECTIVES: The authors compare the toxic effects of iobitridol and iohexol, which are nonionic contrast media with equivalent osmolalities and viscosities on the kidney. METHODS: In a rat acute renal failure (ARF) model, iobitridol or iohexol (both at the dose of 2.87 g I/kg) were injected to rats after pretreatment with indomethacin and N omega-nitro-L-arginin methyl ester. The effects on histopathology, creatinine clearance, and urinary N-acethyl-beta-D-glucosaminidase (NAG) activity were assessed. In a rat renal slice system, the slices were exposed to iobitridol or iohexol (both at the concentration range of 17.5-70 mg iodine/mL) for 60 min. The accumulation of para-aminohippuric acid (PAH), an organic anion, and the intracellular potassium content as the indicators of renal tubular injury were measured to assess the direct effects of iobitridol and iohexol on renal tubules. RESULTS: In the ARF model, no significant difference was detected between the effects of iobitridol and those of iohexol on the creatinine clearance and urinary NAG activity 24 hours after the injection. However, iobitridol produced a lower degree and incidence of renal tubular injury of renal proximal tubules (P < 0.001) and distal tubules (P < 0.05) compared with iohexol. In the rat renal slice system, the iobitridol treatment had significantly less effect on the PAH accumulation compared with iohexol (P < 0.001). There were no changes in the intracellular potassium content. CONCLUSIONS: These findings suggest that iobitridol has significantly less toxic effects on the kidney compared with iohexol under the condition of our experiment.

Analysis of Variance↗

Clearance of iohexol, 51Cr-EDTA and endogenous creatinine for determination of glomerular filtration rate in pigs with reduced renal function: a comparison between different clearance techniques.

In order to simplify and/or improve determination of glomerular filtration rate (GFR) the clearances of iohexol, 51Cr-EDTA and endogenous creatinine were simultaneously determined with different techniques in 21 anesthetized landrace pigs. Their GFR had been reduced to about 1/3 or less of normal GFR. After an intravenous bolus of the GFR markers, their plasma concentration curves were followed for 6 hours with 16 plasma samples. A bladder catheter collected urine during six 60-min periods. The plasma clearance was calculated by dividing "dose of marker" with "area under the plasma concentration curve" (AUC) from the time of injection to infinity using a one- (Clprovisional) and a three-compartment (ClAUC-3comp) model. The renal clearance of iohexol and 51Cr-EDTA was calculated by dividing the amount of marker excreted in the urine in a period by AUC in the same period. The AUC was for iohexol and 51Cr-EDTA determined by integrating the total area in the period (Clren adv)-our reference method representing the "true" GFR and for creatinine determined by using the arithmetic mean of the plasma concentration of the marker at the start and at the end of the urine collection period (Clren simple). Renal clearance of creatinine was significantly lower than renal clearance of iohexol (p = 0.0019) and 51Cr-EDTA (p = 0.0001). There were no significant differences between the renal clearances (Clren adv) of iohexol and 51Cr-EDTA or between their plasma clearances (ClAUC-3comp). For iohexol the median overestimation of the "true" GFR with Clprovisional was higher when "early" plasma samples (30-120 min) were used (4.5 ml min-1 10 kg-1) than when late samples (180-360 min) were used (1.9 ml min-1 10 kg-1). Subtraction of the median extrarenal clearance (known from a study of nephrectomized pigs) from the plasma clearances (ClAUC-3comp) of iohexol and 51Cr-EDTA in pigs with reduced renal function decreased the median overestimation of the "true" GFR from 1.9 to 1.0 ml min-1 10 kg-1 with iohexol and from 1.7 to 0.9 ml min-1 10 kg-1 with 51Cr-EDTA. The plasma clearance technique may be improved in pigs with reduced GFR by (i) including a "late" plasma sample in three- and one-compartment models, which tends to increase the AUC; (ii) introducing a correction formula by normalizing the GFR values of the one-compartment model to those of the three-compartment model, thereby compensating for the rapid early changes in plasma concentration of marker after the bolus injection of the marker; or (iii) subtracting a median (or mean) extrarenal clearance of the marker in pigs from the plasma clearance [according to (i) or (ii)]. The plasma clearance one-compartment technique may be improved in pigs with various levels of GFR values by normalizing the plasma clearance values to the renal clearance values, thereby compensating for both the early changes in plasma concentration of marker and the extrarenal clearance of marker.

Animals↗

Sodium addition and/or oxygen saturation of iohexol during normal and reduced perfusion pressure. Effects on contractile force and risk of ventricular fibrillation in the isolated rabbit heart.

The influence on contractile force (CF) and the propensity for ventricular fibrillation (VF) from infusing the non-ionic contrast medium iohexol during normal (75 cm H2O) and reduced perfusion pressure (35 cm H2O) were investigated in the isolated rabbit heart. Both during normal and reduced perfusion pressure iohexol (150 mg I/ml) with oxygen saturation caused a smaller reduction of CF than iohexol without oxygen. During reduced pressure iohexol with sodium addition (28 mM NaCl) caused less depression of CF than iohexol without sodium. The combination of sodium addition and oxygen saturation had the least influence on CF. Iohexol (350 mg I/ml) without sodium had a similar fibrillatory propensity during both normal and reduced pressure. Enriching iohexol with 28 mM NaCl decreased the risk of VF. The decrease was similar during both normal and reduced pressure. The risk of VF from oxygen saturation of iohexol (350 mg I/ml, without sodium) was similar during both normal and reduced pressure. It is concluded that a small addition of sodium and/or oxygen saturation of a non-ionic monomeric contrast medium have beneficial effects on the heart both during normal perfusion pressure and during ischemia.

Animals↗

Effect on cardiac contractile force from addition of cations and oxygen to iohexol. Comparison with other low-osmotic contrast media in the isolated rabbit heart during normal and reduced perfusion pressure.

The coronary arteries of the isolated rabbit heart were perfused with different contrast media (CM). The effects on cardiac contractile force (CF) from enriching iohexol solutions with sodium, calcium, potassium, magnesium and oxygen were investigated. The effects were studied during normal and reduced perfusion pressure; the latter was intended to simulate flow conditions distal to proximal stenotic processes of the coronary arteries. By adding the above mentioned cations to iohexol (175 mg I/ml) the smallest influence on CF was found when the CM contained 30 mM NaCl, 0.3 mM CaCl2, 0.9 mM KCl and 0.3 mM MgCl2 and this influence on CF was significantly less than caused by iohexol with 30 mM NaCl (p < or = 0.01). The influence on CF was further reduced when this iohexol solution was oxygenated with 100% oxygen (p < or = 0.001). This modified iohexol solution caused a significantly smaller influence on CF than the low-osmotic media iohexol, iopamiro, ioversol and ioxaglate (p < or = 0.001). Ioxaglate caused the greatest decrease in CF of all the CM (p < or = 0.001) and to a greater extent during reduced flow than during normal flow (p < or = 0.01). In conclusion, iohexol enriched with a balanced electrolyte solution and saturated with oxygen had a smaller adverse effect on contractility than iohexol, iopamidol, ioversol and ioxaglate.

Animals↗

Plasma iohexol clearance in automated peritoneal dialysis--its role in adequacy determination.

OBJECTIVE: To compare the relationship of plasma iohexol clearance to standard adequacy measures in an automated peritoneal dialysis (APD) population. DESIGN: Prospective, nonrandomized, open label, simultaneous clearance studies of novel (iohexol) and traditional (urea and creatinine) markers of dialysis quantitation. SETTING: Outpatient peritoneal dialysis units associated with tertiary care university hospitals. PATIENTS: Eighteen stable patients, 13 undergoing continuous cycling peritoneal dialysis (CCPD) and 5 receiving intermittent dialysis, who underwent 24-hour clearance studies were enrolled in and completed the study. INTERVENTIONS: Each subject received 15 mL of iohexol intravenously the morning of a scheduled dialysis night. Blood was obtained for determination of serum concentrations of urea nitrogen and creatinine, and plasma iohexol concentration. Dialysate and urine were collected over 24 hours. MAIN OUTCOME MEASURES: Urea and creatinine data from the total pooled dialysate and from the 24-hour urine collection were used to calculate daily Kt/Vurea and normalized total daily creatinine clearance (CrCl). Total plasma iohexol clearance was calculated using a one-compartment model with the Brochner-Mortensen correction. RESULTS: Normalized [to 1.73 m2 body surface area (BSA)] iohexol clearance correlated very well with normalized CrCl (r2 = 0.777; p < 0.001). A weaker correlation was observed between Kt/Vurea and normalized iohexol clearance (r2 = 0.213; 0.05 < p < 0.1). When data are not normalized using BSA or urea distribution volume, the regressions are improved for both creatinine (r2 = 0.820) and urea (r2 = 0.533). These results were comparable between those on CCPD and those on intermittent therapy. CONCLUSION: Total plasma iohexol clearance provides a simple assessment for APD adequacy by eliminating collection problems inherent to the methodologies currently employed. Such simplicity allows for more frequent assessments of delivered dialysis dose and efficacy of prescription changes.

Blood Urea Nitrogen↗

Clinical testing of iohexol, conray meglumine and amipaque in cerebral angiography.

Iohexol 300 mg I/ml, Conray meglumine 282 mg I/ml and Amipaque 300 mg I/ml have been compared in a randomized double-blind cross over study in which one injection of Iohexol 300 mg I/ml and Conray meglumine 282 mg I/ml was made in the same artery (common and internal carotid artery) of the same patient, and one injection of Iohexol 300 mg I/ml and Amipaque 300 mg I/ml was made in another artery (external carotid artery and vertebral artery). All together 63 cerebral artery branches were examined in 27 patients, who served as their own controls. The effect of the contrast injections on the intra-arterial blood pressure, pulse rate, ECG, circulatory rate and the patients' reactions were recorded under standardized conditions. The quality of the film was also evaluated. No significant difference was found in the cardiovascular effects after the injection of Iohexol or Conray meglumine into the common carotid or internal carotid. There was significantly less pain and sensation of warmth after the injection of Iohexol than after Conray meglumine 282. In the vertebral and the external carotid arteries, where a comparison between Iohexol and Amipaque was carried out, it was found that no significant difference in the cardiovascular effects occurred. There was less sensation of warmth after the injection of Amipaque into the vertebral artery than was caused by Iohexol. The degree of discomfort in form of pain reaction was the same for the two media, when these reactions occurred. No serious side effects were observed.

Adult↗

Use of spiral CT and the contrast medium iohexol to determine in one session aortorenal morphology and the relative glomerular filtration rate of each kidney.

The aim of this study was to determine the relative glomerular filtration rate (GFR), i.e. the GFR of each kidney in percent of total GFR, by spiral CT. In 41 patients, who were part of a follow-up program after endoluminal stent grafting of aortic aneurysm, spiral CT with the contrast medium iohexol was used to evaluate the morphology of the aorta and kidneys. The opportunity was taken to utilize the already injected iohexol to determine the relative GFR with an extra CT sequence. In each patient two determinations were made, 6 or 12 months apart. The amount of a GFR marker accumulating in Bowman's space, tubuli, and renal pelvis within 2-3 min after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was obtained by spiral CT using 10-mm collimation and a table speed of 10 mm/s (pitch ratio 1:1) from the upper to the lower poles. The correlation coefficient between the relative GFR of each kidney determined at the first and second examination was excellent (r=0.99) with a median (range) difference of 1% (0-6%) of total GFR. The radiation dose calculated as the mean absorbed dose to the kidneys was 50 mGy and the effective dose 5 mSv. The morphology of aorta and kidneys and the relative GFR of each kidney can be determined in one session with spiral CT using iohexol as both angiographic contrast medium and as a GFR marker. It is also possible to take some plasma samples in the same session to determine iohexol concentration to calculate the body clearance of iohexol (or take plasma and urine samples to calculate the renal clearance of iohexol).

Aged↗

Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and p-aminohippuric acid.

The objective of this study was to validate a kinetic approach for the simultaneous measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in the dog. Six healthy male Beagle dogs were randomly assigned in a three-period cross-over study of intravenous bolus administration of iohexol (64.7 mg/kg), PAH (10 mg/kg), and an iohexol/PAH mixture. PAH and iohexol were determined simultaneously by a validated high-performance liquid chromatographic method. The iohexol and PAH data obtained after intravenous administration were analyzed using noncompartmental and bicompartmental approaches. A simplified iohexol plasma clearance was also calculated from the terminal elimination phase of the plasma iohexol concentrations versus time profile. The total plasma clearance values for PAH and exo-iohexol were 13+/-2.3 mL/kg/min and 2.9+/-0.3 mL/kg/min, respectively. No significant (or biologically relevant) effect of coadministration of PAH and iohexol was observed on the pharmacokinetic parameters of either drug. The calculation of simplified plasma clearance led to an overestimation of the true plasma clearance. In conclusion, GFR and ERPF can easily and rapidly be measured in the dog by this approach which is relatively noninvasive.

Animals↗

[Validity of iohexol clearance in patients with chronic renal failure and normal renal function in comparison to (99m)Tc-DTPA-clearance].

BACKGROUND AND OBJECTIVE: The most common method used for testing dynamic renal function is creatinine clearance, but it has some limitations, e. g. variable muscle mass and tubular secretion of creatinine. The use of radionuclides as an exact method is limited in terms of availability, cost and time needed for examination. We compared the plasma clearance of iohexol with the established (99m)Tc-diethylenetriaminepentaacetate acid (DTPA) clearance. The aim of the present study was to validate iohexol clearance as a simple and suitable method for measuring to determine GFR with a comparable sensitivity to radioisotopic methods. METHODS: 120 patients (49 females, 71 males), mean age of 56 (range 20 to 84) years with normal renal function and different stages of renal failure, mean creatinine clearance of 61.6 +/- 44,9 (range 1.8 - 181.1) ml/min/1.73 m2 received a bolus injection of 10 ml iohexol, a non-ionic low osmolar x-ray contrast medium. Using the one-compartment model, plasma samples were taken after 150, 240 and 480 minutes. The total plasma disappearance of iohexol was measured by x-ray fluorescence analysis and the clearance was calculated. The (99m)Tc-DTPA clearance was determined in accordance with a standard protocol. RESULTS: A high correlation was found between the clearance of iohexol and (99m)Tc-DTPA (r = 0.95). The average deviation between Iohexol and (99m)Tc-DTPA clearance was 7.4 ml/min/1.73 m2. Allergic and nephrotoxic side effects were not observed. CONCLUSION: Iohexol clearance is a valid method for measuring GFR in patients at any stages of renal failure. It is easy to perform and inexpensive.

Adult↗

Comparison of iohexol and lactulose-mannitol tests as markers of disease activity in patients with inflammatory bowel disease.

Increased intestinal permeability has been proposed as one aetiological factor for inflammatory bowel diseases (IBD). We have previously found that intestinal permeability of a water-soluble contrast medium, iohexol, correlates with disease activity. The objective was to compare the iohexol test with the lactulose-mannitol ratio, which is a more extensively studied permeability marker, in patients with active IBD. Urinary excretion of iohexol was compared to the lactulose-mannitol ratio in 22 patients with an exacerbation of IBD and in 10 healthy controls. Median intestinal absorption of iohexol was 0.64% (range 0.13-3.8%) in the 22 patients and 0.3% (range 0.15-0.54%) in the controls (p = 0.016), whereas the median lactulose-mannitol ratio was 0.037 (range 0.01-0.260) in patients and 0.03 (range 0.004-0.063) in controls (N.S.). Correlation between urinary excretion of iohexol and lactulose-mannitol ratio was positive (R = +0.41, p = 0.018). The urinary excretion of iohexol correlated positively with endoscopic disease activity (R = +0.74, p < 0.001) and the modified Harvey-Bradshaw index (R = +0.44, p = 0.04). The lactulose-mannitol ratio correlated positively with endoscopic disease activity (R = +0.44, p = 0.05), but correlations with clinical index or c-reactive protein were poor. In conclusion, the iohexol test is a superior activity marker compared to the lactulose-mannitol ratio which probably reflects, instead, some pathogenic property of IBD.

Adult↗

Human pharmacokinetics of iohexol. A new nonionic contrast medium.

The pharmacokinetics of iohexol, a new nonionic, water-soluble contrast medium, have been determined after intravenous injection in 20 healthy volunteers, at four different dose levels (125-500 mg I/kg). The apparent volume of distribution was 0.27 1/kg, indicating distribution in the extracellular water. The biologic half-life was 121 minutes, comparable with that of other intravascular contrast media. Iohexol was excreted completely unmetabolized in the urine, with a 100% recovery 24 hours after injection. A comparison of iohexol and chromium-51 (51Cr)-EDTA clearances indicates that iohexol is mainly excreted by glomerular filtration. The 51Cr-EDTA clearance was the same when injected separately and concomitantly with iohexol, indicating that glomerular filtration rate is not affected by iohexol. No dose dependency was observed in the investigated parameters t1/2 alpha, t1/2 beta, Vd, ClT or ClR. Iohexol pharmacokinetics are in correspondence with previously reported data on intravascular contrast media.

Adolescent↗

Glomerular filtration and saturable absorption of iohexol in the rat isolated perfused kidney.

1. The renal handling of iohexol was examined in the rat isolated perfused kidney (IPK) over a perfusate concentration range of 5-20 micrograms ml-1. 2. At a concentration of 5 micrograms ml-1, a ratio of renal clearance over clearance by glomerular filtration (ClR/GF) of 0.63 +/- 0.06 could be determined. This ratio increased until 1.02 +/- 0.06 at 20 micrograms ml-1, indicating that a saturable mechanism is involved in the luminal disappearance of the drug. 3. Pretreatment of the kidneys with polylysine, probenecid or diatrizoate resulted in a significantly enhanced clearance of iohexol, probably due to inhibition of membrane binding. Renal clearance data were fitted to a kinetic model including filtration into the primary urine followed by saturable absorption at the luminal membrane. An absorption constant, KA, of 7.3 +/- 1.3 micrograms ml-1, and a maximum rate of absorption, VA,Max, of 1.4 +/- 0.1 micrograms min-1 were determined. 4. Iohexol accumulated in kidney tissue, reaching a concentration of 2 to 7.5 times the perfusate concentration. In freshly isolated proximal tubular cells and kidney cortex mitochondria, iohexol reduced the uncoupled respiratory rate at a concentration comparable to the highest tissue concentration found in the IPK. 5. In conclusion, iohexol is not only filtered by the kidney but also reabsorbed via a saturable mechanism, which results in tubular accumulation. Intracellularly sequestered iohexol may affect mitochondrial oxidative metabolism. Our results indicate that iohexol is not a true filtration marker.

Animals↗

Lymphography of the thoracic duct by percutaneous injection of iohexol into the popliteal lymph node of dogs: experimental study and clinical application.

OBJECTIVE: To evaluate the efficacy of percutaneous administration of iohexol into the popliteal lymph node as a non-invasive technique for thoracic duct lymphangiography in dogs. STUDY DESIGN: Experimental study and clinical report. ANIMALS: Normal adult dogs (n=4) and 1 dog with recurrent chylothorax. METHODS: For the experimental study, 4 dogs (weight, 8.4-12.3 kg) had 5-10 mL iohexol injected percutaneously into 1 popliteal lymph node and then thoracic radiographs were taken. Popliteal lymph nodes were examined by histopathology 8 days later. One 25-kg dog with recurrent chylothorax had 25 mL iohexol injected into the right popliteal lymph node followed by thoracic radiography. RESULTS: In experimental dogs, the thoracic duct was best visualized on thoracic radiographs after administration of 10 mL iohexol. Clinically, no abnormalities were identified in the injected limb and except for 1 dog that had large numbers of siderocytes and erythrophagocytic macrophages in the injected lymph node, the histopathologic findings in the other injected popliteal lymph nodes were not different from contralateral nodes. In the clinical case, the thoracic duct was visualized, but there was leakage of iohexol around the node. CONCLUSION: The thoracic duct in dogs can be visualized by lymphography after percutaneous injection of iohexol (1 mL/kg at 2 mL/min) into the popliteal lymph node. CLINICAL RELEVANCE: Percutaneous popliteal lymph node administration of iohexol should be considered as an alternative to mesenteric lymph node injection for radiographic identification of the thoracic duct in dogs.

Animals↗