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Biomedical subjects

J J Vallner

Publications and source records attributed to J J Vallner.

At least 37 records · Page 2Linked to original sources
PubMed1979

Dynamic dialysis in drug-erythrocyte interactions.

Application of dynamic dialysis to drug binding to erythrocytes was found to be more complex than previously described. Drug molecules located intracellularly in erythrocytes must diffuse through erythrocytes membranes before diffusing through the dialysis membrane to the external sink in dynamic dialysis. One must consider drug within the dialysis sack and within the erythrocyte and their corresponding volumes. When binding occurs in these internal compartments, different equations result for computing Dt, the total drug within the dialysis bag. With these equations and theoretically generated data, the results of "double dialysis" on the data produced in dynamic dialysis studies of drug-erythrocyte interactions were examined. The intracellular binding of drug by the erythrocyte to a single class of preexisting noninteracting sites could be misinterpreted as cooperative binding, or binding to at least two classes of sites, when the data of dynamic dialysis are treated in the Scatchard format.

Dialysis↗
PubMed1979

Examination of blood clobazam levels and several pupillary measures in humans.

The State-Trait Anxiety Inventory was administered to 15 subjects before initiation of the experiment. Three subgroups of five subjects were defined by computing the unweighted sum of the state and trait anxiety scores. A 40-mg dose of clobazam, a 1.5-benzodiazepine, was administered to each subject and repeated with two additional dosage forms following a 2-week washout period. Blood samples were withdrawn, and blood levels were determined by fluorometric analysis. Additionally, pupillary measures of critical flicker fusion, constriction, and dilation in response to a cognitive task were obtained at 0, 2, 4, and 6 hr. A repeated measures analysis of variance revealed that blood levels were, as expected, statistically different over time and dosage form. The pupillary constriction mirrored the blood levels in statistical patterns. The pupillary measure of cognition related to the anxiety state after the performance effects of the cognitive task were statistically removed. The results suggest that clobazam has less immediate human effect than does diazepam.

Anxiety↗
PubMed1979

Effect of pH on the binding of theophylline to serum proteins.

The binding of theophylline to serum protein within the pH range of 7.0 to 7.8 was determined by equilibrium dialysis using serum from 8 healthy adult volunteers. The percentage of theophylline bound was independent of the total concentration of the drug, but was directly related to pH. Because changes in the free fraction of theophylline may alter the therapeutic response, toxic effects, and pharmacokinetics, any future studies of the pharmacology of theophylline should include assessment of the acid-base status of the patients and measurements of free as well as total theophylline concentrations.

Adult↗
PubMed1979

Influence of respiratory acidosis and alkalosis on volume of distribution of theophylline in dogs.

The volume of distribution of theophylline at nomal pH, and following induction of respiratory acidosis and alkalosis, was studied in four dogs in a three-way crossover design. Although serum half-lives of theophylline varied widely, and acidemia prolonged the time required for distribution equilibration, the volumes of distribution were almost identical for each of the three experimental conditions assuming one compartment pharmacokinetics apply.

Acidosis, Respiratory↗
PubMed1979

Cardiac rhythm disturbances during fiberoptic bronchoscopy: a prospective study.

Twenty-six patients undergoing transnasal fiberoptic bronchoscopy (FOB) were electrocardiographically monitored for 12 hours before, during, and 12 hours after bronchoscopy. We measured arterial lidocaine concentrations during the procedure as well as arterial blood gases before and after the procedure. The incidence of total arrhythmias, including sinus tachycardia, during the control period was 69 percent; minor arrhythmias, 69 percent; and major arrhythmias, 8 percent. During FOB, the incidence of total and minor arrhythmias increased to 77 and 73 percent, respectively; however, the incidence of major arrhythmias decreased to 4 percent. Arterial lidocaine concentrations ranged widely, from 0.1 to 8.7 microgram per milliliter with a mean peak level of 5.0 +/- 0.6 microgram per milliliter, which was reached between 5 and 30 minutes after the insertion of the bronchoscope. We conclude that the incidence of cardiac arrhythmias, excluding sinus tachycardia, during FOB is low and that lidocaine anesthesia probably exerts a protective effect against the development of major arrhythmias during the procedure.

Adult↗
PubMed1978

Plasma levels of clobazam after three oral dosage forms in health subjects.

As can be seen from the tables, the terminal half-life of clobazam is about 50 hours, and from a solid dosage form the peak plasma level occurs approximately 1.5 hours after ingestion. Thus, there is a significant, yet relatively short, dosage form delay effect when the solid dosage forms are compared to the rapidly available solution of the drug. However, based on the areas under the curve, comparison of the solid dosage forms with the solution indicates that the fraction of clobazam absorbed is 1. Pupil diameter measurement at 2, 4, and 6 hours after ingestion of clobazam correlated well with the plasma levels at these times. Pupils were constricted to the highest degree at 2 hours and approached the initial pupillary diameter at the 6-hour measurement.

Administration, Oral↗
PubMed1978

Interaction of sulindac and metabolite with human serum albumin.

The binding of the newly developed nonsteroidal anti-inflammatory agent sulindac and its principal active metabolite, sunlindac sulfide, to human serum albumin was investigated. With the methods of dialysis, fluorescence quenching, and difference spectrophotometry, it was found that both agents were extensively bound to albumin. The binding affinity of the metabolite was considerably higher than that of sunlindac and this effect may be related to its prolonged plasma half-life versus the parent drug. Sulindac binding was albumin concentration dependent, which gave rise to an unfamilar Scatchard analysis of the dialysis data.

Anti-Inflammatory Agents↗
PubMed1977

Liquid chromatography in pharmaceutical analysis VI: determination of dantrolene sodium in a dosage form.

Operating conditions are described for the qualitative and quantitative determination of dantrolene sodium by high-pressure liquid chromatography. A 10-mum porous silica column was employed, using carbon tetrachloride-dimethylformamide (90:10) as the mobile phase. The flow rate was 2.0 ml/min (1800 psig), and the peaks were detected at 375 nm. The analysis of a dosage form can be carried out within 30 min with an accuracy of 3.1%. The results agree favorably with those obtained with a modified spectrophotofluorometric method.

Capsules↗
PubMed1977

Liquid chromatography in pharmaceutical analysis VII: determination of dantrolene sodium in biological fluids.

Dantrolene sodium can be determined in plasma and urine samples by high-pressure liquid chromatography without interference from its two major metabolites, the hydroxy and acetamido compounds. The minimum detectability of the drug using this procedure is 8 ng. The complete assay including extraction, evaporation, and separation steps can be performed in approximately 70 min with an accuracy of 1--3%.

Blood Cells↗
PubMed1977

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↗
PubMed1976

Interaction of dantrolene sodium with human serum albumin.

The binding of dantrolene sodium to human serum albumin was studied by fluorescence quenching and difference spectrophotometry. The association constant was calculated from each method of measurement and was large. This binding affinity may be of importance in the clinical setting, since competitive displacement of anionic drug by concurrently administered agents can occur. Consequently, the displacement of dantrolene from albumin was examined with a wide range of drugs. To gain insight into the characteristics of drug-albumin binding, the interaction of drug with cationic, anionic, and nonionic surfactants was also studied. Additions of drug to solutions of either the anionic or nonionic surfactant failed to result in a perturbation with the difference spectral technique. However, dantrolene added to the cationic resin produced a difference spectrum analogous to that observed with the drug-protein interaction.

Dantrolene↗
PubMed1976

Comparison of graphical and computerized methods for calculating binding parameters for two strongly bound drugs to human serum albumin.

The determination of drug-protein binding parameters (n's and K's) can lead to important information on the required therapeutic dosage regimen and possible clinical complications associated with competitive displacement of one drug by a concurrently administered agent. Graphical and computer estimates of the data are often incorrectly formulated, and and seldom are adequate data obtained at low binding ratios. Commonly used graphical procedures, inadequately formulated computer methods, and a statistically correct computer method were used to compare results obtained from a circular dichroic examination of dicumarol-human serum albumin and fenoprofen-human serum albumin interactions. Literature binding constants for dicumarol-albumin range from 1 X 10(5) to 30 times that figure, and it is shown here that a wide range in parameter estimates may be obtained depending on the method of data analysis. The parameter estimates in the case of fenoprofen-albumin are even more variable.

Binding Sites↗
PubMed1975

Preliminary investigations of intrinsic and extrinsic optical activity as purity criterion for human serum albumins.

Induced circular dichroism measurements were made to follow the binding of four acidic drugs to two lots of crystalline and two lots of fraction V human serum albumins. The magnitude of the induced circular dichroism varied with all lots of albumin, suggesting a strong sensitivity of the phenomenon to small changes in purity or secondary structure of the albumins. The circular dichroism of the albumins themselves showed much less variation. The more classical analytical techniques of UV absorption, measurement of absorption following methyl orange binding, gel electrophoresis, and ultracentrifugation were also performed on the albumins for comparison.

Blood Protein Electrophoresis↗