RESUMEN
Currently, implantable fibrous medical devices still suffer from invisibility under current clinical imaging techniques. To address this problem, 2, 3, 5-triiodobenzoic acid (TIBA) was recruited as a contrast agent, and then a set of iodinated poly(p-dioxanone) (PPDO) fibers was fabricated via melt-spinning hybrid blends of PPDO with TIBA (PPDO/TIBA). The impact of TIBA content on the rheological behavior of blends was evaluated firstly. The physical, chemical, and thermal properties of PPDO/TIBA fibers were investigated accordingly by SEM, FTIR, DSC, and TGA. Moreover, the radiopaque property of PPDO/TIBA hybrid fibers as a potential radio-opacifying platform for medical devices was verified in vitro and in vivo. Finally, the accumulated release results of the hybrid fibers during in vitro degradation indicate the continual X-ray visibility of the hybrid fibers maintains for 22 days. This intriguing iodinated platform may pave the way for constructing fibrous materials with in-situ X-ray tracking property.
Asunto(s)
Medios de Contraste/administración & dosificación , Preparaciones de Acción Retardada/química , Dioxanos/química , Polímeros/química , Ácidos Triyodobenzoicos/administración & dosificación , Medios de Contraste/análisis , Halogenación , Ácidos Triyodobenzoicos/análisis , Rayos XRESUMEN
AIMS: Contrast-induced nephropathy is a commonly encountered problem in clinical practice. The purpose of the study was to design and develop a novel contrast agent, which could be used to prevent contrast-induced nephropathy in the future. METHODS: In total, 20-220nm magnetic nanoparticles were conjugated with iodixanol, and their radio-opacity and magnetic properties were assessed thereafter. Scanning electron microscopy pictures were acquired. Thereafter, the nanoparticles conjugate was tested in cell culture (HUVEC cells), and Quantibody® assay was studied after cell treatment in 1:5 dilutions for 48h, compared with control. RESULTS: The conjugate preparation had an adequate radio-opacity. A 4mm magnetic bubble was attached to a bar magnet and the properties were studied. The magnetic bubble maintained its structural integrity in all angles including antigravity position. Scanning electron microscopy showed magnetic nanoparticles in all pictures and the particles are of 100-400nm agglomerates with primary particle sizes of roughly 20nm. 1:5 diluted particles had no effect on secretion of IL-1a, IL-1b, IL-4, IL-10, IL-13 and TNFa. Particles increased secretion of IL-8 from 24h and 48h. Secretion of IFNg was also increased when particles were added to the cells as early as 1h. Likewise, IL-6 was strongly secreted by HUVEC treated with particles from 24h incubation time. In contrast, the secretion of MCP-1 was slightly reduced on HUVEC treated with particles. CONCLUSION: There is potential for a novel iodixanol-magnetic nanoparticle conjugate to be used in cineradiography. Further investigations need to be performed to study its performance in vitro and in vivo.
Asunto(s)
Cinerradiografía , Medios de Contraste , Nanopartículas de Magnetita , Ácidos Triyodobenzoicos , Quimiocina CCL2/metabolismo , Medios de Contraste/análisis , Medios de Contraste/química , Medios de Contraste/farmacología , Composición de Medicamentos , Evaluación Preclínica de Medicamentos , Dispersión Dinámica de Luz , Conductividad Eléctrica , Ensayo de Inmunoadsorción Enzimática , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interferón gamma/metabolismo , Interleucinas/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Nanopartículas de Magnetita/análisis , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestructura , Microscopía Electrónica de Rastreo , Resonancia Magnética Nuclear Biomolecular , Tamaño de la Partícula , Ácidos Triyodobenzoicos/análisis , Ácidos Triyodobenzoicos/química , Ácidos Triyodobenzoicos/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The administration of iodinated contrast media (CM) can cause microcirculatory disorder leading to acute renal dysfunction. In a prospective, randomized investigation two CM (Iodixanol vs Iopromide) were compared in 16 pigs. Each animal received 10 intra-aortal injections (5 ml Iodixanol or 4.32 ml Iopromide). Microcirculation was assessed using contrast-enhanced ultrasound (CEUS) directly on the kidney surface using time-to-peak (TTP) and blood-volume-analysis. Macroscopic observations were documented. Post mortem residual CM distribution in the kidneys was detected using X-ray. TTP was significantly prolonged over the descending vasa recta of the Iopromide group. This coincided with a visible marble-like pattern on the kidney surface occurring in 30 out of 80 Iopromide-injections but in 4 out of 80 Iodixanol-injections (p = 0.007). The blood volume over the entire kidney did not change after Iodixanol-application, but decreased by about 6.1% after Iopromide-application. The regional blood volume in the renal cortex showed a tendency to decrease by about 13.5% (p = 0.094) after Iodixanol-application, and clearly decreased by about 31.7% (p = 0.022) after Iopromide-application. The study revealed a consistent influence of repeated injections of two different CM on the kidney perfusion using three different imaging methods (CEUS analysis, macroscopic observation and X-ray analysis).
Asunto(s)
Medios de Contraste/análisis , Riñón/diagnóstico por imagen , Animales , Medios de Contraste/efectos adversos , Hemodinámica/efectos de los fármacos , Yohexol/efectos adversos , Yohexol/análogos & derivados , Yohexol/análisis , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Porcinos , Ácidos Triyodobenzoicos/efectos adversos , Ácidos Triyodobenzoicos/análisisRESUMEN
This work reports a simple isocratic hydrophilic interaction liquid chromatographic (HILIC) method for the simultaneous quantification of iodixanol and of its related impurities C, D and E in drug substance. The chromatographic separation was carried out with a Kinetex™ HILIC column, using acetonitrile and formic acid aqueous solution (1.0mmol/L, pH 3.2) (92:08, v/v) as eluent at a flow rate of 0.8mL/min. The autosampler and column temperature were maintained at 20°C and UV detection was set at 243nm. The method was validated in accordance to the ICH guideline and employed for the analysis of two different lots of iodixanol drug substance. The developed method is presented as a valuable alternative to the current methods described in the USP monograph.
Asunto(s)
Ácidos Triyodobenzoicos/análisis , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Interacciones Hidrofóbicas e Hidrofílicas , Indicadores y Reactivos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is diagnosed and explored through the determination of the glomerular filtration rate (GFR). Our goal was to develop a simple LC-MS method for the determination in serum of 2 popular GFR markers, contrast agents iohexol and iothalamate, for routine use and comparison studies between the two markers. A similar contrast agent, ioversol, was used as an internal standard and the method underwent a rigorous validation protocol based on ß-expectation tolerance intervals. METHODS: We adapted the HPLC-UV method from Cavalier et al. to our LC-MS system. Data treatment for the validation was performed using Multiquant 3.0 (Sciex, Framingham, MA, USA) and e.noval 3.0 software (Arlenda, Liège, Belgium). RESULTS: According to the validation results our method will give accurate and reliable results for concentrations ranging from 6.8 to 250µg/ml for iohexol and 6.15µg/ml to 250µg/ml for iothalamate. In our practice these intervals are sufficient to determine both compounds in most patient samples. Samples with higher detected concentrations can always be diluted into range. CONCLUSION: With its internal standard and extensive validation, our method is now ready for routine and clinical research use.
Asunto(s)
Yohexol/análisis , Ácido Yotalámico/análisis , Ácidos Triyodobenzoicos/análisis , Cromatografía Líquida de Alta Presión , Humanos , Yohexol/química , Ácido Yotalámico/química , Espectrometría de Masas , Estándares de Referencia , Ácidos Triyodobenzoicos/normasRESUMEN
The incubation of erythrocytes (RBC) or endothelial cells (HUVEC) in radiographic contrast media (RCM) could induce morphological alterations of or at the cell membranes, e.g. the generation of echinocytes or the formation of stress fibres coinciding with a massive buckling of HUVEC into the vascular lumen, as was demonstrated in several examinations in the recent years. The apposition or embedding of RCM at or in the cell membranes was discussed as possible causative mechanisms because the embedding of molecules into the internal leaflet of the cell membrane bilayer is expected to bulge the cell membrane to the outside, thus inducing e.g. the generation of echinocytes. The examination presented here is based therefore on high resolution scanning electron microscopy (SEM) analyses if iodine as marker element of RCM molecules can be found near the inside of or in RBC membranes (co-localisation study). Morphological analyses exploited secondary electron images (SE) while the analysis of elements exploited either back scattered electrons (BSE) or energy dispersive X-ray analysis (EDX) or the areal display of elements in high lateral resolution in the Bit-map modus. Even at the highest convenient magnification (1:40,000) it was impossible to detect RBC membrane associated iodine (I) after RBC incubation in RCM (Iodixanol, Iopromide) in vitro. Neither in the birds view on the samples nor looking from the side on the freeze fractured samples carrying the RBC was it possible to detect either the signal cohorts typical of I in the sum spectra or the main Lα1-peak in trace analysis.
Asunto(s)
Medios de Contraste/metabolismo , Membrana Eritrocítica/metabolismo , Yohexol/análogos & derivados , Ácidos Triyodobenzoicos/metabolismo , Medios de Contraste/análisis , Membrana Eritrocítica/ultraestructura , Humanos , Yohexol/análisis , Yohexol/metabolismo , Microscopía Electrónica de Rastreo , Radiografía , Ácidos Triyodobenzoicos/análisisRESUMEN
In the present study we evaluated two commonly used iodinated contrast agents, iohexol and iodixanol, as potential markers of impaired renal function. A reversed phase LC-MS method has been developed in order to separate and quantify the two substances. The assay was linear between 0.02 and 9.7 micromol/L for iohexol and between 0.4 and 49.3 micromol/L for iodixanol (r(2) > 0.998). The recovery during sample preparation ranged from 89.1 to 112.4%. The intra- and inter-assay RSD values were 3.06-13.6% for iohexol and 4.32-12.7% for iodixanol. The validated method was subsequently applied to 17 patients scheduled for angiographic procedure displaying normal and impaired renal function. A mixture of iohexol and iodixanol was intra-arterially injected and their corresponding plasma levels were determined periodically over a 24h period following administration. The elimination of both contrast agents followed by the LC-MS approach allowed us to discriminate between patients with normal and impaired renal function at 4, 8 and 24h after administration. Our preliminary results support the predictive value of iohexol and/or iodixanol clearance in a clinical environment to screen and identify patients at risk of developing CIN.
Asunto(s)
Cromatografía Liquida/métodos , Medios de Contraste/análisis , Tasa de Filtración Glomerular , Pruebas de Función Renal/métodos , Espectrometría de Masas/métodos , Medios de Contraste/química , Humanos , Yohexol/análisis , Yohexol/química , Estructura Molecular , Reproducibilidad de los Resultados , Ácidos Triyodobenzoicos/análisis , Ácidos Triyodobenzoicos/químicaRESUMEN
It is important to increase the iodine delivery rate (I), that is the iodine concentration of the contrast material (C) x the flow rate of the contrast material (Q), through a catheter to obtain high quality arteriograms. The iodine delivery rate varies depending on the iodine concentration of the contrast material. The purpose of this study is to estimate the optimum iodine concentration (Copt) of contrast material (i.e. the iodine concentration at which I becomes maximum) through a microcatheter of a given length (L), inner diameter (D) and injection pressure (P). Iohexol, ioversol and iopamidol of 11-12 iodine concentrations (140-350, 160-350 or 160-370 mg cm(-3)) at 37 degrees C are used. I and Reynolds number (Re) of the flow of each contrast material through four microcatheters (0.49-0.68 mm in inner diameter, 1000-1500 mm in length) at injection pressures of 1.38, 2.76, 4.14 and 5.52 x 10(6) Pa (200, 400, 600 and 800 pounds per square inch) are obtained experimentally. The relationships between I and C and between I and Re are examined for each catheter and injection pressure. Copt is 160-280 mg cm(-3) for iohexol, 180-280 mg cm(-3) for ioversol and 200-300 mg cm(-3) for iopamidol. I becomes maximum when Re approximates the critical Reynolds number (Re approximately 2300). Utilizing this principle, we can estimate Copt and its flow rate through a microcatheter of a given L, D and P.
Asunto(s)
Angiografía/instrumentación , Cateterismo/instrumentación , Medios de Contraste/análisis , Análisis de Falla de Equipo/métodos , Inyecciones Intraarteriales/métodos , Yodo/análisis , Reología/métodos , Angiografía/métodos , Cateterismo/métodos , Sistemas de Liberación de Medicamentos/instrumentación , Sistemas de Liberación de Medicamentos/métodos , Inyecciones Intraarteriales/instrumentación , Yohexol/análisis , Yopamidol/análisis , Microinyecciones/instrumentación , Microinyecciones/métodos , Miniaturización , Presión , Control de Calidad , Reología/instrumentación , Sensibilidad y Especificidad , Ácidos Triyodobenzoicos/análisis , ViscosidadRESUMEN
The effect of varying the operating temperature from 6 to 90 degrees C on the chromatographic performance of the exo-exo and exo-endo isomers of the X-ray contrast agent lodixanol in packed-capillary reversed-phase liquid chromatography shows increasing interconversion rates between the two isomeric conformers with increasing temperature. At 90 degrees C, Iodixanol elutes as one sharp peak due to an increased interconversion rate between the two isomeric conformers. Consequently, increased sensitivity is achieved. Temperature programming from 6 to 40 degrees C is utilized to optimize the resolution and determination of the exo-exo and exo-endo isomers. Temperature programming provides a significant decrease in the retention times in comparison with the isothermal separations while still preserving baseline separation of the isomers.
Asunto(s)
Cromatografía Liquida/métodos , Medios de Contraste/análisis , Ácidos Triyodobenzoicos/análisis , TemperaturaRESUMEN
UNLABELLED: PURPOSE, MATERIAL AND METHODS, AND RESULTS: The dialyzability of the high-molecular X-ray contrast medium iodixanol was examined in an in vitro hemodialysis model using two different hollow fiber membranes: one high-flux (poly-sulfone) membrane and one intermediate-flux (cellulose triacetate) membrane. Blood flow was 200 ml/min and membrane area 1.3 m2. The dialyzer clearance of iodixanol dissolved in a mixture of leukocyte-filtered SAG-M blood and compatible citrate plasma was 134.2 +/- 3.6 ml/min for the polysulfone membrane and 113.0 +/- 3.6 ml/min for the cellulose triacetate membrane. CONCLUSION: Iodixanol is readily dialyzed through commercial high-flux membranes.
Asunto(s)
Medios de Contraste/aislamiento & purificación , Diálisis Renal/métodos , Ácidos Triyodobenzoicos/aislamiento & purificación , Celulosa/análogos & derivados , Medios de Contraste/análisis , Creatinina/análisis , Estudios de Evaluación como Asunto , Filtración/instrumentación , Soluciones para Hemodiálisis/análisis , Humanos , Técnicas In Vitro , Membranas Artificiales , Polímeros , Diálisis Renal/instrumentación , Sulfonas , Ácidos Triyodobenzoicos/análisisRESUMEN
Iodixanol (Visipaque, 320 mgI/ml) was compared with iopamidol (Solutrast, 370 mgI/ml) in a double-blind, randomized, parallel group, intravenous DSA phase-III trial for evaluation of safety and efficacy. A total of 117 patients received iodixanol (n = 60) or iopamidol (n = 57). Diagnostic efficacy was evaluated using categoric and visual analogue scales. Discomfort and adverse events were recorded. A total of 39 patients collected urine up to 72 h after the examination for analysis. Diagnostic efficacy and radiographic density were similar in both groups. Discomfort was milder with iodixanol. The difference between the frequency of adverse events between both groups (iodixanol = 7, iopamidol = 2) was without statistical significance. Creatinine clearance was slightly more affected by iodixanol, whereas the increase in renal excretion of N-acetyl-beta-glucosaminidase (NAG) in the first 24-h collection period after the examination was significantly higher (p < 0.01) with iopamidol. Iodixanol was of equal diagnostic efficacy compared with iopamidol despite its reduced iodine content. Both contrast media are well suited for IV DSA.
Asunto(s)
Angiografía de Substracción Digital , Aorta Abdominal/diagnóstico por imagen , Medios de Contraste , Yopamidol , Pierna/irrigación sanguínea , Ácidos Triyodobenzoicos , Acetilglucosaminidasa/orina , Adulto , Angiografía de Substracción Digital/efectos adversos , Aortografía , Arterias , Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos , Medios de Contraste/análisis , Creatinina/sangre , Creatinina/orina , Método Doble Ciego , Femenino , Humanos , Inyecciones Intravenosas , Yodo/análisis , Yopamidol/administración & dosificación , Yopamidol/efectos adversos , Yopamidol/análisis , Riñón/efectos de los fármacos , Riñón/enzimología , Masculino , Persona de Mediana Edad , Dolor/etiología , Seguridad , Sensación , Ácidos Triyodobenzoicos/administración & dosificación , Ácidos Triyodobenzoicos/efectos adversos , Ácidos Triyodobenzoicos/análisisRESUMEN
The origin of 4-acetyl-2-[N-acetyl-3,5-bis(2,3-dihydroxypropylcarbamoyl)- 2,4,6-triiodoanilinomethyl]-5,7-diiodo-3,4-dihydro-2H-benzo[1,4]ox azine- 6,8-dicarboxylic acid bis(2,3-dihydroxypropylamide) = N-acetyl cyclized iodixanol, 2-[N-acetyl-3,5-bis-(2,3-dihydroxypropylcarbamoyl)-2,4,6- triiodoanilinomethyl]-5,7-diiodo-3,4-dihydro-2H-benzo[1,4]oxazine- 6,8-dicarboxylic acid bis(2,3-dihydroxypropylamide) = cyclized iodixanol and 5,5'-(N-acetyl-2-hydroxypropane-1,3-diyldiamino)bis[N,N'-bis(2,3- dihydroxypropyl)-2,4,6-triiodoisophthalamide] = deacetyl iodixanol in the manufacturing process of the X-ray contrast agent 3,3',5,5'-tetrakis(2,3-dihydroxypropylcarbamoyl)-2,2',4,4',6,6'-++ +hexaiodo- N,N'-(2-hydroxypropane-1,3-diyl)diacetanilide = iodixanol is discussed and their synthesis and purification are described. Their physical and toxicological properties, and analytical and spectroscopic data are summarized.
Asunto(s)
Medios de Contraste/síntesis química , Ácidos Triyodobenzoicos/síntesis química , Animales , Cromatografía Líquida de Alta Presión , Medios de Contraste/análisis , Medios de Contraste/toxicidad , Inyecciones Intravenosas , Isomerismo , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Ácidos Triyodobenzoicos/análisis , Ácidos Triyodobenzoicos/toxicidadRESUMEN
RATIONALE AND OBJECTIVES: The authors compared the safety and pharmacokinetics of Iotrolan (water-soluble) in hysterosalpingography (HSG) with those of Lipiodol (oil-soluble). METHODS: Iotrolan and Lipiodol were administered intraperitoneally at doses of 100 mg iodine/kg to female rabbits. Retention in the body was investigated by x-ray imaging, plasma kinetics, and urinary and fecal excretion. Irritability in the abdomen was investigated by histologic examination. RESULTS: Iotrolan was entirely excreted into the urine within 2 days after administration. Conversely, Lipiodol was excreted into the urine, had a half-life of 50 days, and was retained for more than 21 days in the abdomen. Iotrolan induced no inflammatory reaction in the abdomen, whereas Lipiodol induced a marked abdominal inflammatory reaction, including granuloma formation. Iotrolan had no effect on iodine concentration in the thyroid; Lipiodol increased iodine concentration significantly. CONCLUSIONS: Iotrolan, which is a water-soluble and nonionic dimeric contrast medium, has potential greater safety for use in HSG than Lipiodol.
Asunto(s)
Medios de Contraste/farmacocinética , Histerosalpingografía , Aceite Yodado/farmacocinética , Ácidos Triyodobenzoicos/farmacocinética , Abdomen/patología , Animales , Líquido Ascítico/inducido químicamente , Líquido Ascítico/patología , Heces/química , Femenino , Granuloma/inducido químicamente , Semivida , Inyecciones Intraperitoneales , Yodo/análisis , Aceite Yodado/efectos adversos , Aceite Yodado/análisis , Irritantes/efectos adversos , Conejos , Radiografía Abdominal , Seguridad , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Ácidos Triyodobenzoicos/efectos adversos , Ácidos Triyodobenzoicos/análisis , Ácidos Triyodobenzoicos/sangre , Ácidos Triyodobenzoicos/orinaRESUMEN
Iodixanol (Visipaque) is a new nonionic roentgen contrast medium intended for general use. Visipaque is a pharmaceutical formulation of iodixanol which is isotonic and iso-osmotic with blood. Two synthetic routes from 5-nitro-isophthalic acid to iodixanol are described. The chemical structure is confirmed spectroscopical data ((1)H-NMR, (13)C-NMR, FAB-MS, UV, IR and Raman). Chromotographic characteristics are related to the isomerism of iodixanol.
Asunto(s)
Medios de Contraste/síntesis química , Ácidos Triyodobenzoicos/síntesis química , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ácidos Triyodobenzoicos/análisis , Ácidos Triyodobenzoicos/químicaRESUMEN
The iodine-specific detection techniques X-ray fluorescence spectrometry, neutron activation analysis and radiochemical detections of (125)I-labelled substance are well suited for quantification of iodixanol in biological samples. The limit of detection is 60 microgram iodixanol/ml for X-ray fluorecence analysis and 1 to 10 microgram iodixanol/ml for neutron activation analysis. Reversed-phase high-performance liquid chromatography (HPLC) has been employed when selective determination of iodixanol was needed for identificational purposes or when quantification of very small amounts of iodixanol was essential. An optimized HPLC method for quantification of iodixanol in rat serum and urine is presented. The limit of detection for this method is 0.20 microgram iodixanol/ml for rat serum and 3.0 microgram iodixanol/ml for rat urine. When samples were analyzed by HPLC and thin layer chromatography, no metabolites of iodixanol were observed in rat, monkey or human urine, or in rat kidney and bile. Studies with equilibrium dialysis and HPLC determination of iodixanol showed no protein binding of the contrast agent in human plasma; the 95% confidence interval for the result was 0.0+/-2.1%.
Asunto(s)
Medios de Contraste/análisis , Ácidos Triyodobenzoicos/análisis , Animales , Cromatografía Líquida de Alta Presión , Humanos , Macaca fascicularis , Masculino , Análisis de Activación de Neutrones , Unión Proteica , Ratas , Ratas Wistar , Espectrometría por Rayos X , Ácidos Triyodobenzoicos/metabolismoRESUMEN
RATIONALE AND OBJECTIVES: The authors established a rat model of the twitching reaction to contrast media in striated muscle and investigated the influence of nonionic contrast medium on the twitching reaction regarding the nonionic dimer iodixanol compared with the monomer iohexol and the dimer iotrolan. The authors also studied the influences from the electrolyte additions of iodixanol. METHODS: The interval from start of contrast medium injection to start of head movement was compared for iohexol (140 and 350 mg iodine/mL), iodixanol (150 and 320 mg iodine/mL), and iotrolan (300 mg iodine/mL). Comparison was made with mannitol and mannitol containing the same electrolyte concentrations as iodixanol (150 and 320 mg iodine/mL). RESULTS: No differences in latency period were found between iohexol 140 mg iodine/mL (isotonic) and 350 mg iodine/mL (880 mOsm/kg). Iodixanol caused a lesser effect on the twitching reaction than the iohexol solutions and iotrolan. When the electrolytes of iodixanol were added to mannitol (300 mOsm/kg), there was a later onset of the twitching reaction than with electrolyte-free mannitol. CONCLUSIONS: Differences in latency period caused by a change in osmolality were not found. The interval for a twitching reaction was longer with iodixanol than with iohexol, iotrolan, and iso-osmolar mannitol. The weak effect of the iodixanol solution was probably partially caused by the electrolyte content.
Asunto(s)
Medios de Contraste/efectos adversos , Discinesia Inducida por Medicamentos/etiología , Yohexol/efectos adversos , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Ácidos Triyodobenzoicos/efectos adversos , Animales , Cloruro de Calcio/análisis , Medios de Contraste/análisis , Medios de Contraste/química , Femenino , Cabeza/fisiopatología , Yohexol/análisis , Yohexol/química , Masculino , Manitol/química , Manitol/farmacología , Concentración Osmolar , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Cloruro de Sodio/análisis , Ácidos Triyodobenzoicos/análisis , Ácidos Triyodobenzoicos/químicaRESUMEN
A fully automated high-performance liquid chromatographic method has been developed for the analysis of the radiographic contrast agent iopentol in human plasma and whole blood. This method is based on on-line sample preparation with dialysis followed by pre-column enrichment of the dialysate. The method was compared with a manual sample preparation method based on protein precipitation with tetrahydrofuran. The inter-assay and intra-assay variations and the limits of quantitation were the same for both methods. The on-line combination of dialysis and column-switching high-performance liquid chromatography was shown to be a reliable and time-saving technique for monitoring iopentol in human whole blood and plasma.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Plasma/química , Ácidos Triyodobenzoicos/análisis , Ácidos Triyodobenzoicos/sangre , Diálisis/métodos , HumanosRESUMEN
The pharmacokinetic properties of the x-ray contrast medium, iodixanol, a new nonionic dimer, were investigated in a phase I study including 40 healthy male volunteers. Iodixanol (300 mg I/mL) was administered intravenously (i.v.) at four dose levels--0.3, 0.6, 0.9, and 1.2 g iodine (I)/kg body weight--and saline was given as a control. 51Cr-EDTA was given concomitantly with iodixanol at all dose levels to study renal excretion of iodixanol. Mean half-lives were 26 and 131 minutes in the distribution and elimination phase, respectively. Apparent volume of distribution was 0.28 1/kg body weight, indicating distribution to extracellular fluid only. Within 24 hours after injection, 97% of the dose was excreted unmetabolized in the urine via glomerular filtration. The excretion in feces was 1.2% of the dose. The parameters calculated were independent of the given dose. The pharmacokinetics of iodixanol are comparable with those reported for other intravascular contrast media.
Asunto(s)
Medios de Contraste/farmacocinética , Ácidos Triyodobenzoicos/farmacocinética , Adulto , Biotransformación , Radioisótopos de Cromo , Medios de Contraste/administración & dosificación , Medios de Contraste/análisis , Relación Dosis-Respuesta a Droga , Ácido Edético , Heces/química , Tasa de Filtración Glomerular , Humanos , Inyecciones Intravenosas , Masculino , Tasa de Depuración Metabólica , Factores de Tiempo , Ácidos Triyodobenzoicos/administración & dosificación , Ácidos Triyodobenzoicos/análisisRESUMEN
A simple, accurate and precise high-performance liquid chromatographic method for determination of iopentol in urine and serum is presented. The modifications of the method necessary for the determination of some other non-ionic contrast agents and in other biologic fluids are also presented.