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PubMed2005

Development and validation of an HPLC-UV method for determination of iohexol in human plasma.

An HPLC-UV analytical method for estimation of iohexol in human plasma was developed and validated. Protein precipitation and iohexol extraction from plasma (100 microl) was carried out by adding 800 microl perchloric acid (5%, v/v in water) containing iohexol related compound B as the internal standard followed by vortex mixing and centrifugation. The supernatant (90 microl) was then injected onto a microBondapak C(18) column (150 mm x 3.9 mm, 10 microm) maintained at 30 degrees C. The mobile phase comprised of various proportions of acetonitrile and water with a total run time of 12 min and the wavelength of the UV detector was set at 254 nm. The extraction recovery of iohexol from plasma was >95% and the calibration curve was linear (r(2)=0.99) over iohexol concentrations ranging from 10 to 750 microg/ml (n=8). The method had an accuracy of >92% and intra- and inter-day CV of <3.7% and <3.6%, respectively. The method reported is simple, reliable, precise, accurate and has the capability of being used for determination of iohexol in clinical settings.

Blood Chemical Analysis↗
PubMedDate not supplied

Experiences with iohexol and iodixanol during cardioangiography in an unselected patient population.

AIM: To compare the frequency of adverse events after cardioangiography with iohexol and iodixanol in an unselected patient population with special regard to previously defined "risk patients": age> or =65 years, severe coronary artery disease, unstable angina pectoris and left ventricular dysfunction. METHODS: A total of 1020 patients referred to cardioangiography were included in this open, prospective cross-sectional study, comparing iodixanol (320 mgI/ml) and iohexol (350 mgI/ml). Adverse events were recorded and the patients answered a questionnaire. RESULTS: Cardiac adverse events (CAE) i.e., angina pectoris, arrhythmia and dyspnea within 24 h of examination were reported by 9% of patients receiving iohexol and by 7% receiving iodixanol. Two cases of ventricular fibrillation occurred, both after iohexol. The proportion of CAE was 11% for patients> or =65 years receiving iohexol and 7% in younger patients. For patients receiving iodixanol the proportion was 7%, in both age groups. Patients with severe coronary disease had more CAE than less ill patients in both CM groups. The proportion of unstable patients with CAE was 18% in the iohexol group and 12% in the iodixanol group. Left ventricular dysfunction was not related to CAE. CONCLUSIONS: Iodixanol could be advantageous in patients with unstable angina.

Adolescent↗
PubMed1989

Age dependence of renal function: clearance of iohexol and p-amino hippurate in healthy males.

Iohexol, a newly developed non-ionic contrast agent, has been recently documented as a reliable glomerular filtration marker. This study describes the age dependence of the single injection clearance of iohexol in a sample of healthy male volunteers ranging from 21 to 77 years of age. In parallel, renal plasma flow was studied by measuring the total clearance of p-amino hippuric acid administered as a continuous infusion. In subjects older than 50 years a negative correlation to age was found for both p-amino hippuric acid and iohexol clearance, with a reduction of 52 ml/min and 12 ml/min per decade, respectively, whereas no age dependence was found for younger subjects. Correlation between p-amino hippuric acid and iohexol clearances was 0.81. However, the filtration fraction, defined as the ratio of iohexol to p-amino hippuric acid clearance, was higher in the elderly subjects. A consistent discrepancy was found between total and renal clearances of p-amino hippuric acid, indicating significant renal metabolism. Renal clearance of creatinine was poorly correlated to iohexol clearance and did not show any relationship to age.

Adult↗
PubMed1999

Improved clearance of iohexol with longer haemodialysis despite similar Kt/V for urea.

BACKGROUND: The efforts to improve the quality of haemodialysis (HD) has renewed the interest in the consequences of blood-flow distribution for removal of solutes. METHODS: To test the effects of HD time per se, 10 patients were studied in a cross-over fashion with HD for 3 h and 1 week later for 6 h, with similar blood urea Kt/Vs, achieved by adjusting the blood flow rate to 290 and 120 ml/min respectively. Injections of iohexol (MW 821 Dalton) were given 2 days prior to the dialysis sessions. Blood samples were taken before, during (6/HD), 1 and 24 h after the HD and analysed for concentrations of urea and iohexol. A urea on-line monitor (Gambro) was used for continuous recordings and sampling of dialysate. RESULTS: According to the study design the blood Kt/V for urea (Daugirdas II) was similar for 3 and 6 h HD, close to 1.0 (n.s), while the removed mass of urea showed that Kt/V was slightly and significantly higher for the 6 h HD. The 'apparent' mass of iohexol, defined as plasma concentration times estimated distribution volume, fell to 29% and 21% of pre-dialysis levels after 3 h and 6 h HD, respectively (P<0.01), but increased after HD, and more so after the short dialysis, reaching 46% of the predialysis mass 24 h after 3 h HD vs. 36% after 6 h HD (P<0.05). The removed mass of iohexol was 920+/-110 mg with 6h HD and 700+/-81 mg with 3h HD, (P<0.01). Thus, the longer dialysis removed 32% more iohexol despite similar blood Kt/V for urea. CONCLUSION: The treatment time per se affects solute removal despite similar blood Kt/V for urea. This is particularly true for an intermediate-size molecule like iohexol.

Aged↗
PubMedDate not supplied

The effect of iohexol on glucose metabolism compared with metrizamide.

In a previous in vitro study we demonstrated reduced CO2 production in rat hippocampal tissue when metrizamide was added. This metabolic depression is believed to be a result of the 2-deoxy-D-glucose (2-DG) portion of the metrizamide molecule since 2-DG is a known competitive inhibitor of glucose metabolism. This competitive inhibition probably occurs at the cell membrane since it has never been shown that metrizamide penetrates neural cells. Further the inhibition is most likely related to competition for the membrane glucose carrier. A new nonionic contrast medium, iohexol, does not contain a 2-DG component and if the hypothesis for the metabolic inhibition is valid we should not expect metabolic inhibition with iohexol. This hypothesis was tested using the rat hippocampus model previously used for metrizamide. We compared iohexol with metrizamide in isotonic concentrations and also examined the effect of hypertonicity. These experiments did not demonstrate inhibition of CO2 production with iohexol at near physiologic osmolalities, however, there was a marked depressive effect with increasing osmolality. This effect from hypertonicity is, however, probably of less importance in vivo where water will rapidly diffuse toward the hypertonic areas. The apparent lack of interference of the iohexol molecule on glucose metabolism should therefore make iohexol a more suitable contrast medium, for subarachnoid investigations than metrizamide.

Animals↗
PubMedDate not supplied

Iohexol cerebral angiography. Multicenter clinical trial.

Ionic contrast media currently used in cerebral angiography frequently cause discomfort due to hyperosmolality. This double-blind, multicenter trial compared two ionic media, meglumine iothalamate and meglumine-Na diatrizoate, with the new nonionic agent, iohexol, in 277 patients undergoing cerebral angiography. Vital signs, cardiovascular changes, and neurologic status were evaluated before, during, and after injection. Patients were observed for adverse reactions for up to 24 hours following studies. Patient discomfort and image quality were evaluated. Visualization was good or excellent with all media studied. No significant physiological differences were observed between the ionic and iohexol groups, but fewer iohexol patients experienced large increases (greater than 20 mmHg) in systolic blood pressure. Iohexol patients experienced significantly less discomfort; ionic patients reported severe discomfort 21/2 times more often. This finding was attributed to iohexol's low osmolality. Iohexol may be indicated particularly for use in selective angiograms where discomfort is a factor and for patients suspected of having blood-brain barrier disruption.

Adult↗
PubMed1988

Urine profiles following intravenous diatrizoate, iohexol, or ioxilan in rats.

The effects of intravenous diatrizoate, iohexol, ioxilan, or saline on albumin, glucose, sodium and the enzymes N-acetyl-beta-D-glucosaminidase (NAG), lactate dehydrogenase (LDH), and L-gamma-glutamyltransferase (GGT) in the urine of 24 normal Wistar rats were followed for seven days. During the first two hours after administration of diatrizoate, all profile components changed markedly; the albumin excretion was significantly greater than following ioxilan and iohexol; glucose, LDH, and GGT excretions were significantly greater than following ioxilan. Iohexol and ioxilan caused a higher excretion of albumin, LDH, and GGT than saline. Iohexol also increased glucose and sodium levels. Glucose and GGT were significantly higher following iohexol than following ioxilan. Both high osmolar and low osmolar contrast media may cause temporary glomerular and tubular damage. Urine profile components are affected most by diatrizoate, less by iohexol, and least by ioxilan.

Animals↗
PubMed1991

A comparison of iohexol and diatrizoate-meglumine in children undergoing cardiac catheterization.

Iohexol (Omnipaque) and meglumine and sodium diatrizoate (Renografin-76) were compared in a double-blind, randomized study for their efficacy, safety, and hemodynamic effects as angiographic contrast agents in children. Forty-four children were randomly allocated to receive either iohexol or diatrizoate as a component of their routine or emergency cardiovascular evaluation. Following age stratification, baseline physiologic parameters were not significantly different between patients receiving either iohexol or diatrizoate. After systemic ventricular injection, iohexol produced significantly less hemodynamic alteration in systemic systolic blood pressure, systemic ventricular end-diastolic pressure, and dP/dt. Less alteration in heart rate and significantly less effect on the QT interval were seen with iohexol. Image quality was comparable, although significantly more patient mobility was associated with diatrizoate-meglumine. This study shows that iohexol, a nonionic contrast medium, causes less hemodynamic disturbance than diatrizoate-meglumine in children. Therefore, its use to be preferred in these potentially high-risk patients.

Adolescent↗
PubMed1991

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↗
PubMed1993

Urine profiles and kidney histologic findings after intravenous injection of mannitol and iohexol in the degeneration phase of gentamicin nephropathy in rats.

RATIONALE AND OBJECTIVES: Previous studies have shown that iodinated contrast media may cause further renal dysfunction in tubulointerstitial nephropathy induced by gentamicin. The current investigation was undertaken to study whether the dysfunction after intravenous injection of a low-osmolar contrast medium is due to a chemotoxic and/or an osmotic effect. METHODS: Urine profiles were followed for 3 or 9 days after intravenous injection of saline, mannitol, and varying dosages of iohexol (1, 2.5, 5, and 10 mL/kg body weight (BW); 350 mg I/mL) in 60 rats, in which intramuscular injection of 40 mg/kg BW gentamicin had been administered daily nine times. A seventh group of 10 rats was given 20 mg/kg BW gentamicin and 5 mL/kg BW of 350 mg I/mL iohexol. Another 10 rats injected with saline served as controls. RESULTS: Both mannitol and iohexol increased the excretion of albumin and the enzyme N-acetyl-B-D-glucosaminidase (NAG) temporarily; the effect was independent of the dose of iohexol. There was a dose-dependent effect on the transient increase in excretion of the enzymes lactate dehydrogenase (LDH), gamma glutamyltransferase (GGT), and alkaline phosphatase (ALK); mannitol did not increase the excretion of these enzymes. In the group given 20 mg/kg BW gentamicin, only the dose-dependent effects of iohexol were seen. Neither various plasma components nor light/electron microscopy showed any changes that could solely be related to the contrast medium. CONCLUSIONS: Iohexol produces transient renal effects in gentamicin nephropathy, which may be due to both chemotoxic and osmotic mechanisms.

Animals↗
PubMed1999

A comparison of the plasma disappearance of iohexol and 99mTc-DTPA for the measurement of glomerular filtration rate (GFR) in diabetes.

BACKGROUND: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy. GFR is most commonly measured by the plasma clearance of radioisotopes, however, use of iohexol, a non-ionic radiocontrast medium, is a recently described alternative and has shown good agreement with inulin clearance. A one-compartment model is used for calculating GFR in most Australian centres but a two-compartment model is more accurate. AIMS: To set up a non-radioisotopic method for assessment of GFR using iohexol, and to compare this with the currently used 99mTc-diethylene-triamine-penta-acetic acid (DTPA) method. Secondly, to compare GFR results using an unmodified one-compartment model with a one-compartment model subjected to the Brochner-Mortensen modification. METHODS: Twenty-one patients with diabetes had assessment of GFR with simultaneous measurements of 99mTc-DTPA and iohexol plasma clearance. Plasma clearance was determined by the slope intercept method and then modified according to the Brochner-Mortensen equation. Plasma iohexol concentrations were determined by capillary electrophoresis. RESULTS: There was no significant difference between iohexol and 99mTc-DTPA derived GFR values, difference 4.3+/-7.7 mL/minute (mean+/-SD). This was despite 99mTc-DTPA protein binding demonstrated in the range of 5-10%. Comparison of GFR results using an unmodified one-compartment model with a Brochner-Mortensen corrected one-compartment model showed higher GFR values with the former, in the range of 20-30% for GFR values > 100 mL/minute. CONCLUSION: Iohexol provides an efficient alternative to radioisotopic methods for serial measurement of GFR in diabetic patients with hyperfiltration, incipient and overt nephropathy. A one-compartment model with its inherent overestimation of GFR should be replaced by the Brochner-Mortensen modified one-compartment model.

Adult↗
PubMed1994

Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations.

We evaluated iohexol as a filtration marker in 150 children. The clearance of iohexol was compared with that of inulin or with a formula clearance. The single-sample clearance of iohexol showed a good correlation with the clearance of inulin (r = 0.834). The clearance of iohexol correlated well (r = 0.672) with the formula clearance. The optimal blood sampling time for iohexol clearance determinations appears to be between 120 and 180 min after injection, at least in patients with relatively normal filtration rates. We conclude that iohexol clearance is an accurate method of determining the glomerular filtration rate in clinical practice.

Child, Preschool↗
PubMed1996

Measurement of glomerular filtration rate using nonradioactive Iohexol: comparison of two one-compartment models.

Radioisotopic methods for the determination of the glomerular filtration rate (GFR) are highly accurate but require the collection of multiple blood and urine samples and are costly to perform due to personnel, material, and analysis costs. Nonradioactive methods of GFR determination have the potential of minimizing procedure costs while preserving accuracy. We determined the GFR simultaneously by 125I-iothalamate and nonradioactive iohexol clearance methods in 41 adults. The study group consisted of 54% males, with a mean age of 50.7 (range 28-79) years and a mean GFR by 125I-iothalamate clearance of 66.5 +/- 28.3 (range 10-118) ml/min. The iohexol concentrations were measured by a simplified high-performance liquid chromatography method that did not require sample preparation. The iohexol plasma clearance was calculated by both a new one-compartment model as well as by Jacobsson's one-compartment model. Using Jacobsson's single-sample model and data from the 240-min point, there was an excellent correlation between 125 I-iothalamate and nonradioactive iohexol clearance values: r2 = 0.95, standard error of the estimate = 11.4 ml/min, and intrapatient coefficient of variation = 16.9%. However, this formula tended to overestimate GFRs < 30 ml/min and to underestimate GFRs > 80 ml/min. The new one-compartment model is a modification of Bubeck's model, originally used for the determination of renal plasma blood flow. Using this modified model, there was an excellent correlation between 125I-iothalamate and nonradioactive iohexol clearance values at all levels of GFR tested: r2 = 0.95, standard error of the estimate = 9.2 ml/min, and intrapatient coefficient of variation = 13.7%. In conclusion, the determination of the plasma clearance of iohexol by a nonradioactive technique and a monoexponential model is a simple and accurate method of determining the GFR in patients with varying degrees of renal impairment.

Adult↗
PubMed1993

[Central effects of iohexol and iopamidol, non-ionic contrast media].

Central effects of intravenously (i.v.)-administered iohexol were compared with those of iopamidol in a series of tests. Mannitol was used as a reference. As assayed by the primary screening test based on Irwin's method, i.v. administration of mannitol resulted in a score of 0 in ddY mice and a score of 0.6 in ICR mice in the startle response. These results were not different from the data of both iohexol and iopamidol. Iopamidol at a dose of 1750 mgI/kg produced an inhibitory effect on the spontaneous locomotor activity. Iohexol at a dose of 7000 mgI/kg potentiated the duration of thiopental-induced narcosis. Hypothermia was caused by high doses of both iohexol and iopamidol. Electric stimulus increased the mortality of mice pretreated with high doses of iohexol and iopamidol. Both drugs had no notable activities in the anticonvulsant, electroencephalic, muscle relaxant and antinociceptive tests. These results indicate that both iohexol and iopamidol do not necessarily possess a similar pharmacological action. Judging from the LD50 of approximately 15000 mgI/kg for both drugs, they seem unlikely to have a specific pharmacological action on the central nervous system.

Animals↗
PubMed1998

A comparison of a non-ionic dimer, iodixanol with a non-ionic monomer, iohexol in low dose intravenous urography.

A prospective, double-blind study of 392 patients randomized into four groups was performed to establish whether diagnostic intravenous urograms could be obtained with a lower dose of iodine when using the dimeric, non-ionic contrast medium iodixanol compared with the monomeric, non-ionic iohexol. Patients received iodixanol or iohexol containing either 9 or 12 g of iodine (gI). The primary parameter was the diagnostic quality of the 6 min film, assessed in a blinded fashion, by consensus, by four radiologists. Iodixanol at both doses was diagnostic in over 90% of cases. Iohexol was only diagnostic in 74% (9 gI) and 81.8% (12 gI). Pairwise comparisons revealed that iodixanol 9 gI was significantly better than both iohexol 9 gI (p = 0.0005) and 12 gI (p = 0.014). No significant difference was present for different doses within the same contrast medium group. Iodixanol resulted in poorer bladder distension than iohexol. Iodixanol caused significantly less discomfort than iohexol.

Adult↗
PubMed1995

Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate.

Renal clearance of inulin is the best available indicator of GFR but cannot be used routinely for clinical purposes and is also difficult to perform for clinical investigation when repeated measurements are required. The aim of this study was to find a reliable alternative to inulin clearance that would allow one to avoid the use of radioactivity and problems related to the continuous infusion of the marker. The plasma clearance of unlabeled iohexol, a nonionic contrast agent, was used. Forty-one patients (creatinine clearance 6 to 160 mL/min per 1.73 m2) underwent simultaneous measurements of renal clearance of inulin and plasma clearance of iohexol. Iohexol was given as a single iv dose, and blood samples were drawn up to 600 min after the administration. Iohexol concentrations (by HPLC) were analyzed by a two-compartment, open-model system. A highly significant correlation between the plasma clearance of iohexol and the renal clearance of inulin over a wide range of GFR values was found. By analyzing the data with a simplified method that uses a one-compartment model corrected with the Bröchner-Mortensen formula, an excellent correlation with the inulin clearance was also observed. When only patients with moderate to severe renal failure were considered, a significant correlation between the two methods was found. A further comparison between GFR determined with iohexol and iopromide, a new low-osmolarity, low-viscosity contrast medium, was also performed in a subgroup of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Risk factors associated with development of seizures after use of iohexol for myelography in dogs: 182 cases (1998).

OBJECTIVE: To determine prevalence of seizures after use of iohexol for myelography and identify associated risk factors in dogs. DESIGN: Retrospective study. ANIMALS: 182 dogs that received iohexol for myelography in 1998. PROCEDURE: Medical records were reviewed for age, breed, sex, weight, dose and total volume of iohexol, injection site, number of injections, lesion type and location, total duration of anesthesia, duration from time of iohexol injection to recovery, presence and number of seizures, and whether surgery followed the myelogram. RESULTS: 39 (21.4%) dogs had at least 1 generalized seizure during or after myelography. Injection site was strongly associated with prevalence of seizures, and risk of seizure was significantly higher after cerebellomedullary injections, compared with lumbar injections. Mean total volume of iohexol administered to dogs that had seizures was significantly higher, compared with that administered to dogs that did not have seizures, although dosage did not differ between groups. Weight was significantly correlated with risk of seizure, and dogs that weighed > 20 kg (44 lb) had higher prevalence of seizures than dogs that weighed < 20 kg. CONCLUSIONS AND CLINICAL RELEVANCE: It is preferential to administer iohexol via the L5-6 intervertebral space to minimize the risk of seizures. Higher prevalence of seizures in large dogs, compared with smaller dogs, may be caused by administration of larger total volumes of contrast agent per volume of CSF.

Animals↗
PubMed1990

Determination of glomerular filtration rate using iohexol clearance and capillary sampling.

Glomerular filtration rate can be conveniently quantified by monitoring the plasma clearance of iohexol. In this study we have evaluated the possibility of further simplifying the investigation by using capillary sampling. Eight women and two men were given a single injection of iohexol (5 ml Omnipaque). Three to 4 h after the injection plasma and capillary samples were taken. Iohexol concentrations in whole blood and in plasma were measured by high-performance liquid chromatography after precipitation with perchloric acid. Iohexol in blood was quantitatively distributed to the plasma compartment. Plasma concentrations of iohexol calculated from the capillary blood concentration and erythrocyte volume fraction were in good agreement with actual plasma concentrations (r = 0.98). The imprecision of iohexol determination in capillary samples was 3.5% (CV) and clearance measurements using venous and capillary sampling also agreed well.

Adult↗