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Biomedical subjects

H W Jun

Publications and source records attributed to H W Jun.

At least 55 records · Page 3Linked to original sources

Formation of a cyclic derivative of ethacrynic acid with diazomethane.

Samples of ethacrynic acid were treated with methanol-hydrochloric acid or with diazomethane. GLC and mass spectrometric analysis indicated that the methanol-hydrochloric acid reaction gave the expected methyl ester, whereas diazomethane treatment gave a compound containing an additional 14 mass units. Accurate mass measurement and PMR and IR spectra showed that this product was a cyclic derivative of the methyl ester of ethacrynic acid, methyl 4-(2,3-dihydro-4-ethyl-5-furyl)-2,3-dichlorophenoxyacetate. Either derivatization method can be used for development of an assay for ethacrynic acid.

Chromatography, Gas↗

GLC determination of methenamine in tablets.

A rapid and sensitive GLC method was developed for the quantitative determination of methenamine in tablets. The method was shown to possess several advantages over the official NF assay. After dissolution of the whole tablet in absolute ethanol and addition of an internal standard (pentylenetetrazol), an aliquot was injected into the gas chromatograph for analysis. The sample was chromatographed using a stainless steel column packed with 10% OV-17 on Chromosorb W-HP. Quantitation was achieved by measuring peak heights. The simplicity, directness, extreme rapidity, and accuracy of the method represents an improvement over the official method and the other proposed assays.

Chromatography, Gas↗

Plasma level studies of penbutolol after oral dose in man.

Plasma levels of penbutolol (HOE 893d) were determined in eight healthy adult male subjects after oral administration of 50-mg capsules. Fast absorpiton of the drug from the gastrointestinal tract was indicated by the rapid increase in plasma levels during the absorption phase, with a peak time at about 1 hour after dosing in all subjects. After the peak level, plasma concentrations declined biexponentially, with an average half-life of 2.5 and 27 hours for the fast and slow disposition phases, respectively. These values were in good agreement with data previously found for this drug. Cumulative excretion of intact drug in the urine of the eight subjects during 72 hours after dosing was less than 4 per cent, except for one subject who excreted 9.82 per cent of the dose. Large individual variations were found for area under the plasma level curves, disposition rates, and amounts of intact drug excreted in the urine. Significant pharmacologic effects were noted in all eight subjects at the 50-mg dose level, and mild side effects were evident in one half of these subjects. The average drop in blood pressure and pulse rate for all subjects was 26/18 mm Hg and 19 beats per minute, respectively.

Administration, Oral↗

Nitrofurantoin solubility in aqueous urea and creatinine solutions.

Experiments were carried out to determine the effect of urea and creatinine on the solubility of nitrofurantoin in water at different temperature and pH conditions. The addition of urea to aqueous media increased nitrofurantoin solubility up to a maximum concentration level and then decreased solubility at higher urea concentrations. The amount of urea needed to bring about maximum nitrofurantoin solubility was dependent on temperature and ranged between 1.75 and 2.50%. Spectral studies suggest a possible interaction between urea and nitrofurantoin molecules. Nitrofurantoin solubility increased with an increasing creatinine concentration ranging from 0.05 to 1.6%. Spectral studies indicate a strong interaction between creatinine and nitrofurantoin molecules in solution. The combined effect of urea and creatinine of the solubility of nitrofurantoin could account for the absence of crystalluria with this drug, even though unusually high concentrations in urine have been reported.

Buffers↗

Pharmacokinetic studies of pentylenetetrazol in dogs.

Pharmacokinetic profiles of pentylenetetrazol in the dog were studied following rapid intravenous and oral administrations of a convulsant dose (15-20 mg/kg). Plasma level-time curves after a rapid intravenous injection showed biexponential decline, indicating that the disposition of this drug in the dog follows a two-compartment body model. Pharmacokinetic parameters were calculated from the intravenous data. After oral administration of the solution dose, the peak plasma level appeared at about 30 min postdose, indicating that the absorption occurs rapidly. Areas under the oral plasma level-time curves s howed that the drug was absorbed completely and that the first-pass metabolism effect was minimal. The ligation studies of the kidney and the liver suggested that the main elimination pathway of this drug was biotransformation in the liver. The average plasma half-life was 1.4 hr. At steady state, the volume of distribution was approximately equivalent to the volume of the total body water.

Administration, Oral↗

Drug-biomolecule interactions: fluorescence studies on interaction of aminonaphthalenesulfonic acid derivatives with serum albumins.

The binding of the three aminonaphthalenesulfonic acid derivatives to human and bovine serum albumins was studied by measuring the fluorescence enhancement of the compounds. The number of binding sites of human and bovine serum albumins for these compounds appears to be one and two, respectively, under the experimental conditions. As the molar ratio of the fluorescent compounds to bovine serum albumin increased, the binding sites appeared to increase for the compounds. The quenching of the native fluorescence of albumin was examined by the successive addition of methanolic solutions of these compounds. 1-Anilinonaphthalene-8-sulfonate quenched the protein fluorescence to a greater extent than the other compounds studied, indicating that 1-anilinonaphthalene-8-sulfonate molecules are bound more closely to the tryptophan residues of albumin. The finding that the three compounds did not quench the fluorescence of tryptophan dissolved in water indicates no direct molecular interaction between tryptophan and the three fluorescent probes. The driving force for binding may be due to the structural characteristics of the amino acid sequence surrounding the tryptophan residues.

Anilino Naphthalenesulfonates↗

Quantitative GLC determination of pentylenetetrazol in biological fluids.

A quantitative, sensitive, and specific GLC method was developed for the determination of pentylenetetrazol in water, plasma, and urine. The assay involves a single extraction of the sample into chloroform followed by centrifugation, evaporation, and chromatography. The method for pentylenetetrazol is reproducible, and the sensitivity limit of the assay is 0.5 mug of pentylenetetrazol/ml of biological fluid using a 2-ml sample. This method has a sensitivty sufficient to detect human plasma levels after therapeutic clinical doses and was successfully applied to monitor complete plasma level profiles of this drug in dogs. The data indicate that this drug is very rapidly absorbed following an oral dose, and the half-life of the drug in plasma is approximately 1 hr.

Administration, Oral↗