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[A method for the simultaneous determination of iothalamic acid and creatinine clearance by coupled-column liquid chromatography].

[125I]iothalamic acid clearance is used for the estimation of glomerular filtration rate. Therefore, we developed a coupled-column liquid chromatography for the simultaneous determination of iothalamic acid and creatinine in human serum and urine samples to calculate their clearance. The liquid chromatograph consisted of an automatic injector, four columns and four switching valves. Timing of sample injection and switching of valves were controlled by a combination of timer units. Diluted samples were injected into a column of weakly acidic ion exchanger (Asahipak ES-502C, 30 degrees C, C1), and iothalamic acid excluded from the column was purified by gel chromatography on a hydrophilic gel (Asahipak GS-320H, 50 degrees C, C2) and then by ion exchange chromatography on a weakly basic anion exchanger (Asahipak ES-502N, 50 degrees C, C3). Creatinine that was eluted from C1 after iothalamic acid was transferred to Asahipak GS-320H (37 degrees C, C4) and C1 was backflushed until 10 min before the next sample was injected. Samples were injected every 55 min. The mobile phase was a sodium propionate buffer prepared by dissolving 0.035 mol of NaOH and 0.35 mol of propionic acid in 1 kg of ultra pure water, and its flow rate was 1.1 ml per min. Creatinine clearance calculated from the data obtained by this method was higher than that obtained by Jaffé's method, because serum creatinine concentrations obtained by this method were lower than those obtained by Jaffé's method. Iothalamic acid clearance (y) calculated from the data on serum and urine samples of clearance time 105-135 min showed a close correlation with inulin clearance (x) calculated from the data obtained by the anthrone method, for which aliquots of the same samples were used (y = 1.066 x -1.429 ml/min, r = 0.997, n = 15).

Chromatography, Liquid

High-performance liquid chromatographic determination of iothalamic acid in human plasma and urine.

A simple, rapid and sensitive method for the determination of iothalamic acid (IA) in both plasma and urine is reported. After extraction with ethyl acetate, IA was determined by strong anion-exchange high-performance liquid chromatography with ultraviolet detection at 254 nm. The lower limit of detection was 0.5 micrograms/ml. The average recovery was 73 and 57% from plasma and urine, respectively. Linearity was found over the investigated concentration range (up to 500 micrograms/ml for plasma and up to 10.0 mg/ml for urine). The reproducibility of the technique was good (coefficient of variation less than 6%) as was the precision and accuracy (coefficient of variation less than 2.5%). No interference from endogenous substances or any of the common drugs tested was found.

Acetates

Effect of methylglucamine salts of iocarmic and iothalamic acids on hemodynamics, acid-base equilibrium and coagulation.

The effects of electrolytes, osmolality, pH, PaO2, PaCO2, hematocrit, blood volume and coagulation occurring after a rapid intra-aortic injection of a monomer and a dimer (salts of methylglucamine of the iothalamic and iocarmic acids) were compared. The effects of the monomer agreed with previous results but the effects of the dimer differed from those reported in the literature.

Acid-Base Equilibrium

Preparation and evaluation of radiopaque hydrogel microspheres based on PHEMA/iothalamic acid and PHEMA/iopanoic acid as particulate emboli.

Highly porous poly(2-hydroxyethyl methacrylate) (PHEMA) microspheres prepared by suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) in presence of polymeric diluents such as poly(methyl methacrylate) (PMMA) in toluene and poly(tetramethylene glycol) (PTMG) were made radiopaque by esterification of the reactive hydroxyl groups with iothalamic acid and iopanoic acid, two radiopaque substances clinically used. Of the various solvents and catalysts examined, tetrahydrofuran (THF) and N,N'-dimethyl paratoluidine (DMPT) were found to be best for obtaining a high degree of conversion. More than 30 wt% iodine could be bound to the microspheres which made them sufficiently radiopaque to be imaged radiographically. Microspheres retained their porosity, swelling ability, hydrophilicity, and surface morphology to a significant extent after iodination. Preliminary implantation studies of such microspheres subcutaneously in rats have shown no adverse tissue reactions over a 6-month period. It is suggested that these microspheres would prove to be useful as particulate emboli in endovascular embolization.

Animals

Uptake of contrast materials by experimental acute myocardial infarctions: a preliminary report.

The concentration of iodine within infarcted and normal myocardium after intravenous administration of contrast material was determined by fluorescence excitation analysis in seven dogs at 48 hours after coronary arterial ligation. The iodine concentration of infarcted myocardial tissue was several times greater than normal myocardium after administration of meglumine/sodium diatrizoate, iodipamide, and an experimental polymer of iothalamic acid.

Acute Disease

Solute excretion during intravenous urography: a comparison of sodium and methylglucamine iothalamates.

The sodium and methylglucamine salts of iothalamic acid were compared as urographic agents. The two drugs were administered intravenously to dogs at a dose of 600 mgI/kg. The outputs and concentrations of the major urinary solutes and the injected solutes were measured to define the differences in renal excretion of sodium and methylglucamine iothalamates. The action of methylglucamine as a relatively inert osmotic diuretic was reconfirmed. When sodium iothalamte was adminstered the tubular reabsorption of sodium and chloride was greater than when methylglucamine iothalamate was used. It is suggested that this reabsorption explains the advantage of sodium-linked agents over methylglucamine-linked agents in urography.

Animals

[Enoxacin concentration in seminal fluid, in prostate secretions and in prostatic adenoma tissue following oral administration or intravenous infusion].

In eleven volunteers and 39 patients undergoing transurethral resection of the prostate or bladder tumor, concentrations of enoxacin were measured in seminal fluid (volunteers), in prostatic fluid (volunteers, patients) and in prostatic adenoma tissue (patients) after oral (400 mg) administration and intravenous (428 mg) infusion (60 min) of enoxacin. Simultaneously 2.534 g of iothalamic acid was i.v. injected to identify possible urinary contamination. The concentrations of enoxacin in seminal fluid after 2-4 h and in prostatic tissue after about 1-4 h and 14-16 h exceeded plasma concentrations more than two-fold. The concentrations in prostatic fluid after 1-4 h were about half the plasma concentrations. Venous blood samples were taken after intravenous infusion at intervals of up to 24 h in a total of 14 patients. The mean plasma concentration of enoxacin decreased from its maximum of 6.9 mg/l at the end of infusion to 0.5 mg/l at 12 h after administration. A terminal half life of 6.65 h was calculated according to an open two-compartment model.

Administration, Oral

Study of renal functions by repeated constant infusion of radiotracers before and after initiation of therapy in hypertension or in diabetes mellitus.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were simultaneously measured by obtaining an isotopic steady state during a continuous infusion of 125I orthoiodohippurate (OIHA). A good correlation was found between the clearances of Ioth (y) and of inulin or polyfructosan (x) : y = 1.18 X (x) + 8.43 (r = 0.96; P less than 0.001) and between the clearances of OIHA (y') and of PAH (x') : y' = 0.62 X (x') + 21.2 (r = 0.93; P less than 0.001). When renal functions were impaired the use of Ioth was not convenient since the infusion time necessary to reach a radioactive plateau was longer than 3 hours. On the contrary, excellent results were obtained by using OIHA. In this case, the main advantages were the absence of urine collection and the rapid obtention of an isotopic equilibrium. The repeated determination of renal clearances in hypertensive or diabetic patients appears to be useful in the study of changes induced by antihypertensive drugs or insulin. Clearances were slightly improved by clonidine, claimed to be useful in hypertension associated with chronic renal failure. GFR and ERPF were rapidly increased by insure on the metabolic and hemodynamic changes induced by insulin than on the return to normal of glomerular basement membrane permeability.

Adrenergic alpha-Antagonists