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K Prodanova

Publications and source records attributed to K Prodanova.

7 recordsLinked to original sources
PubMed1999

Protein binding of piroxicam studied by means of affinity chromatography and circular dichroism.

The protein binding of piroxicam, a widely used non-steroidal anti-inflammatory drug has been investigated by high-performance liquid affinity chromatography, with phenylbutazone and diazepam used as markers for binding-site characterization, and by circular dichroism titration. It was found that piroxicam binds to high-affinity phenylbutazone-binding sites and to high-affinity diazepam-binding sites. No binding to the low-affinity sites of either marker was established. High values of the primary (high-affinity) binding constants corresponding to both types of binding site were obtained by means of a mathematical method cited in the literature. The circular dichroic spectra of piroxicam were studied at a given albumin concentration and various drug concentrations. A new Cotton effect was observed and was ascribed to the binding of piroxicam to the protein molecule. The values of differential molar ellipticity (delta theta) were treated by a new mathematical procedure for analysis of the data obtained. A high affinity constant was calculated for one class of binding site. Its value is in good agreement with the values obtained by affinity chromatography. These results reveal that circular dichroism is an acceptable method for investigation of protein binding.

Binding Sites↗
PubMed1998

New mathematical procedure for analysis of data obtained by means of circular dichroism titration method.

A new approach for analysis of circular dichroism titration data for the investigation of drug-protein binding is proposed. The molar ellipticity change and the total drug concentration are considered as a function of the concentration of unbound (free) drug. A new minimization algorithm for estimating the number of classes of binding sites and the association constants is developed. The proposed algorithm offers a statistical criterion to choose the best model for fit of experimentea data. In addition the given procedure estimates the concentration of umbound drug.

Algorithms↗
PubMed1991

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin.

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats. An increase of digoxin serum levels and changes in some basic pharmacokinetic parameters of digoxin (t1/2 alpha, t1/2 beta, AUC, AL) were established in gentamicin-pretreated rabbits, the changes being dependent on the dose and schedule of administration. Most pronounced were the changes in digoxin kinetics during simultaneous 5-day treatment with digoxin (0.035 mg/kg i. p.) and nontoxic doses (10 and 2 mg/kg) of gentamicin. The toxicity of digoxin in guinea-pigs, assessed by lethal doses of digoxin, was increased only after the highest dose of gentamicin (100 mg/kg), while after nontoxic or close to therapeutic doses (10 and 2 mg/kg) of gentamicin the digoxin toxicity was not changed or was even decreased. Digoxin decreased the nerve-muscle blocking effect of gentamicin on cat ischiadicus-gastrocnemius preparation. The possible mechanisms involved are discussed.

Animals↗
PubMed1988

Pharmacokinetics of vephylline--a new N-substituted theophylline derivative.

Vephylline (7,2-bis-2-hydroxyethylamino-1, 3-dimethylxanthine tartarate) is a xanthine derivative with high bronchodilating activity, low toxicity, and weak effects on the central nervous system. The aim of this study is to determine the pharmacokinetic parameters of vephylline after intravenous and oral (in solution and in tablets) administration to rabbits. Vephylline (dose 50 mg/kg b.w. intravenousely and orally in solution and dose 53.5 mg/kg b.w. in the form of tablets) is administered to the rabbits in an autocontrol crossover design at 7-days intervals. After the intravenous administration the distribution is relatively fast (t1/2 alpha = 3.28h). High values of the apparent volume of distribution--12.15 1/kg suggest tissue accumulation. Elimination is considerably slower (t1/2 beta = 19,00 h) than distribution. After oral administration of the drug in solution the absorption half-life is short and the bioavailability is relatively high. Peak plasma levels are attained at the first hour. The differences in the distribution and elimination patterns for vephylline and theophyline could determine a longer effect for the new bronchodilating drug. The results are discussed in regard to the future clinical application of vephylline.

Administration, Oral↗
PubMed1985

Correlations between the pharmacological effects and the pharmacokinetic behaviour of tetraminol.

Tetraminol (trans-2-hydroxyethylamino-3-hydroxy-5,8-dimethoxy-1,2,3, 4-tetrahydronaphthalene hydrochloride) is a newly synthesized antihypotensive agent. Its pressor activity is accompanied by a compensatory slowing down of heart rate. Changes in plasma levels after intravenous administration of 1 and 2 mg/kg b.w. to rats and rabbits can be fitted to a two-compartment open pharmacokinetic model (previous communications). Experiments were carried out with simultaneous registration of effects on blood pressure (R1) and heart rate (R2). Mathematical treatment of data for R1 and R2 revealed that changes with time can be described by biexponential equations of the type: R1i = A1i.e-a1it+B1i..e-a21t. Three different ways to correlate the data from the pharmacological and pharmacokinetic experiments were tried: 1) For the time interval during which the pharmacological response changes in the range Rimax- 20 to Rimax- 80% there exists a linear relationship with a high degree of statistical significance between the changes in the effects and plasma levels. 2) In the lambda 1-phase of the drug distribution there also exists a linear relationship between the effects and plasma levels. This is so because Tetraminol exhibits its pressor effect by direct stimulation of alpha-adrenergic receptors in the walls of the peripheral blood vessels. 3) Most suitable for expressing the relationship which exists between the pharmacological effects and the plasma concentration of Tetraminol for the entire time interval is the nonlinear function of the type: Ri/(Rimax - Ri) = QiCsi.

Animals↗
PubMedDate not supplied

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin.

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats. An increase of digoxin serum levels and changes in some basic pharmacokinetic parameters of digoxin (t1/2 alpha t1/2 beta, AUC, C1) were found in gentamicin-pretreated rabbits, the changes being dependent on the dose and schedule of administration. The most pronounced changes were those in digoxin kinetics during simultaneous 5-day treatment with digoxin (0.035 mg/kg i.v.) and nontoxic (10 and 2 mg/kg) doses of gentamicin. The toxicity of digoxin in guinea-pigs, assessed by administration of lethal doses of digoxin, was increased only after the highest dose of gentamicin (100 mg/kg), while after nontoxic or close to therapeutic doses (10 and 2 mg/kg) of gentamicin, the digoxin toxicity was either unchanged or even decreased. Digoxin decreased the nerve-muscle blocking effect of gentamicin on cat ischiadicus-gastrocnemius preparation. The possible mechanisms involved are discussed.

Animals↗