digoxin and gitoxin

The positive inotropic effect of 16 alpha-gitoxin was studied in 52 female and male healthy volunteers between the ages of 21 and 27 years and a body weight between 55 and 76 kg after the single i.v. injection or oral administration in doses between 2.5 and 15 mg. The inotropic effect was evaluated by the use of the systolic time intervals (left ventricular ejection time, LVET, and electromechanic systole, QS2) and by the QT-Interval of the ECG. The glycoside plasma level was measured simultaneously to the pharmacodynamic parameters by a radioimmunoassay, 16 alpha-gitoxin abbreviated dose-dependently the STI (LVET and QS2) for 30 (i.v.) or 15 ms (per os) and the QT interval for 35 ms. A mean plasma concentration of 401 ng/ml was measured 15 minutes after the i.v. injection of 5 mg and a mean plasma level of 402 ng/ml was measured 1 hour after the oral intake of 10 mg 16 alpha-gitoxin as an aqueous-ethanolic solution. The shortening of the STI-values and of the QT-interval correlated with the administered glycoside dose and with the AUC0-6-value. The AUC-values increased linearly with the administered dose. The ratio of the AUC0-6-values after i.v. or oral administration of 7.5 mg 16 alpha-gitoxin amounted to 0.673. Doses of 16 alpha-gitoxin which induce a maximum abbreviation of STI or QT did neither provoke a distinct decrease in heart rate nor cardiac disturbances. Sixteen-alpha-gitoxin develops a positive inotropic effect within a few minutes after i.v. injection and also after oral intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Cardiac Glycosides; Cardiotonic Agents; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Injections, Intravenous; Male; Radioimmunoassay

We developed a highly sensitive and selective reversed-phase HPLC-pulsed amperometric detection (RP-HPLC-PAD) method for cardiac glycoside detection. Eight cardiac glycosides were completely separated within 45 min on a reversed-phase column using a water-acetonitrile gradient, and were detected using a PAD under NaOH alkaline conditions. The detection (S/N=3) and quantification (S/N=10) limits for the cardiac glycosides were 0.1-0.3 and 0.3-0.8 ng, respectively. The linear regression coefficient was 0.9962-0.9998 for concentrations of 1-25 μg/mL. Cardiac glycosides in the Digitalis purpurea leaf displayed intra- and inter-day precisions (RSDs) of <9.30% and average recoveries of 98.63-99.94%. The contents of gitoxin, digitonin, and digitoxin in the D. purpurea were 0.197, 0.11, and 0.379 mg/g for leaf dried at 60 °C, 0.058, 0.11, and 0.090 mg/g for leaf dried at ambient temperature, and N.D. (not detected), and 18.379 mg/g, N.D. for seed, respectively. We conclude that our method shows good precision and accuracy.

Topics: Acetonitriles; Cardiac Glycosides; Chemistry Techniques, Analytical; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Digitalis; Digitonin; Digitoxin; Digoxin; Electrochemistry; Models, Chemical; Plant Leaves; Reproducibility of Results; Solvents; Temperature

This work reports the use of simple coacervates of the hydrophobic protein zein to encapsulate Gitoxin, a cardiotonic glycoside. The microspheres obtained using ethanol, methanol, iso-propyl alcohol were characterized using viscosity index, scanning electron microscopy (SEM) and laser light scattering particle analyzer. Scanning electron micrographs indicated that the zein film was made of microspheres with diameter in the 1-1.5 microm range, which could be controlled. Sizes of Gitoxin-loaded zein microspheres changed little before and after release of the drug because of conglutination among zein microspheres. Release of Gitoxin from zein microspheres, were performed in vitro to investigate the mechanism of model drug release. The results show that the zein microspheres obtained using ethanol are best suited for use as a sustained-release form of Gitoxin. The microspheres may also be useful in drug targeting system since the diameter of the microspheres is appropriate for phagocytosis by macrophages. Both zein film and Gitoxin-loaded zein microsphere film were effective in suppressing platelet adhesion.

Topics: Cardiotonic Agents; Cell Adhesion; Delayed-Action Preparations; Digoxin; Drug Delivery Systems; In Vitro Techniques; Kinetics; Lasers; Light; Materials Testing; Microspheres; Particle Size; Scattering, Radiation; Viscosity; Zein

Inhibition of Na+/K+-ATPase activity from human erythrocyte membranes and commercial porcine cerebral cortex by in vitro single and simultaneous exposure to digoxin and gitoxin was investigated to elucidate the difference in the mechanism of the enzyme inhibition by structurally different cardiac glycosides. The drugs exerted a biphasic dose-dependent inhibitory effect on the enzyme activity in both tissues, supporting the existence of two sensitive Na+/K+-ATPase isoforms. The IC50 values for the low and high affinity isoforms were calculated from the inhibition curves using mathematical analysis. The Hill coefficient (n) fulfilled the relationship 1 < n < 3, suggesting cooperative binding of inhibitors to the enzyme. Kinetic analysis showed that digoxin and gitoxin inhibited Na+/K+-ATPase by reducing the maximum enzymatic velocity (Vmax) and Km, implying an uncompetitive mode of interaction. Both the isoforms were always more sensitive to gitoxin. The erythrocyte enzyme was more sensitive to the inhibitors in the range of low concentrations but the commercial cerebral cortex enzyme exerted a higher sensitivity in high inhibitors affinity concentration range. By simultaneous exposure of the enzyme to digoxin and gitoxin in combinations a synergistic effect was achieved by low inhibitor concentrations. An antagonistic effect was obtained with erythrocyte membrane enzyme at high inhibitors concentration.

Topics: Animals; Cerebral Cortex; Digoxin; Dose-Response Relationship, Drug; Enzyme Activation; Erythrocyte Membrane; Humans; Kinetics; Molecular Conformation; Sodium-Potassium-Exchanging ATPase; Structure-Activity Relationship; Swine

Recent research has shown the anticancer effects of digitalis compounds suggesting their possible use in medical oncology. Four extracts obtained from the leaves of Digitalis purpurea subsp. heywoodii have been assessed for cytotoxic activity against three human cancer cell lines, using the SRB assay. All of them showed high cytotoxicity, producing IC50 values in the 0.78 - 15 microg/mL range with the methanolic extract being the most active, in non toxic concentrations. Steroid glycosides (gitoxigenin derivatives) were detected in this methanolic extract. Gitoxigenin and gitoxin were evaluated in the SRB assay using the three human cancer cell lines, showing IC50 values in the 0.13 - 2.8 microM range, with the renal adenocarcinoma cancer cell line (TK-10) being the most sensitive one. Morphological apoptosis evaluation of the methanolic extract and both compounds on the TK-10 cell line showed that their cytotoxicity was mediated by an apoptotic effect. Finally, possible mechanisms involved in apoptosis induction by digitalis compounds are discussed.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Cardenolides; Cell Line, Tumor; Digitalis; Digoxin; Etoposide; Humans; Inhibitory Concentration 50; Kidney Neoplasms; Phytotherapy; Plant Extracts; Plant Leaves

Antibody 26-10, obtained in a secondary immune response, binds digoxin with high affinity (K(a) = 1.3 x 10(10) M(-1)) because of extensive shape complementarity. We demonstrated previously that mutations of the hapten contact residue HTrp-100 to Arg (where H refers to the heavy chain) resulted in increased specificity for digoxin analogs substituted at the cardenolide 16 position. However, mutagenesis of H:CDR1 did not result in such a specificity change despite the proximity of the H:CDR1 hapten contact residue Asn-35 to the cardenolide 16 position. Here we constructed a bacteriophage-displayed library containing randomized mutations at H chain residues 30-35 in a 26-10 mutant containing Arg-100 (26-10-RRALD). Phage were selected by panning against digoxin, gitoxin (16-OH), and 16-acetylgitoxin coupled to bovine serum albumin. Clones that retained wild-type Asn at position 35 showed preferred binding to gitoxin, like the 26-10-RRALD parent. In contrast, clones containing Val-35 selected mainly on digoxin-bovine serum albumin demonstrated a shift back to wild-type specificity. Several clones containing Val-35 bound digoxin with increased affinity, approaching that of the wild type in a few instances, in contrast to the mutation Val-35 in the wild-type 26-10 background, which reduces affinity for digoxin 90-fold. It has therefore proven possible to reorder the 26-10 binding site by mutations including two major contact residues on opposite sides of the site and yet to retain high affinity for binding for digoxin. Thus, even among antibodies that have undergone affinity maturation in vivo, different structural solutions to high affinity binding may be revealed.

Topics: Acetyldigoxins; Animals; Antibodies, Monoclonal; Arginine; Binding Sites; Crystallography, X-Ray; Digoxin; Enzyme-Linked Immunosorbent Assay; Genetic Vectors; Haptens; Kinetics; Mice; Models, Chemical; Mutagenesis, Site-Directed; Mutation; Protein Binding; Serum Albumin; Valine

Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl chain at C-3 of the steroid nucleus (10) were prepared from gitoxin (1). The pharmacological activities of the resulting compounds (4 and 10) were evaluated by measurement of inhibitory effect on NA+, K(+)-adenosine triphosphatase (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated guinea-pig papillary muscle preparations, and the effect on smooth muscle using the mesenteric artery from spontaneously hypertensive rats. Most of the compounds showed a smaller contractile effect on the arterial muscle. Among these compounds, gitoxin 3"-nitrate (4g) exhibited the most desirable biological activities, such as PIE comparable to that of 1, 1.25 times wider concentration-dependent range than 1, and lack of contractile activity on vascular muscle.

Topics: Animals; Bufanolides; Cardiotonic Agents; Digoxin; Dogs; Guinea Pigs; Kidney; Muscle Contraction; Muscle, Smooth, Vascular; Plants, Medicinal; Rats; Sodium-Potassium-Exchanging ATPase; Stimulation, Chemical; Structure-Activity Relationship

New immunometric forms of immunoassay are much more flexible to use than competitive-format immunoassays for small molecular analytes. An example of the utility of this flexibility is the ability to wash the capture antibody after it has been exposed to analyte but before addition of the labeled reagent. This simple maneuver has a large impact on the specificity obtained from already highly specific assays. We also show that specificity can be further increased by means of our multiple binding assay approach, in which the final reading reflects analyte binding to two different primary capture monoclonal antibodies.

Topics: Antibodies, Monoclonal; Digitoxigenin; Digitoxin; Digoxigenin; Digoxin; Immunoassay; Sensitivity and Specificity; Strophanthidin

We determined the sequence, specificity for structurally related cardenolides, and three-dimensional structure of the anti-digoxin antibody 40-50 Fab in complex with ouabain. The 40-50 antibody does not share close sequence homology with other high-affinity anti-digoxin antibodies. Measurement of the binding constants of structurally distinct digoxin analogs indicated a well-defined specificity pattern also distinct from other anti-digoxin antibodies. The 40-50-ouabain Fab complex crystallizes in space group C2 with cell dimensions of a = 93.7 A, b = 84.8 A, c = 70.1 A, beta = 128.0 degrees. The structure of the complex was determined by X-ray crystallography and refined at a resolution of 2.7 A. The hapten is bound in a pocket extending as a groove from the center of the combining site across the light chain variable domain, with five of the six complementarity-determining regions involved in interactions with the hapten. Approximately three-quarters of the hapten surface area is buried in the complex; two hydrogen bonds are formed between the antibody and hapten. The surface area of the antibody combining site buried by ouabain is contributed equally by the light and heavy chain variable domains. Over half of the surface area buried on the Fab consists of the aromatic side-chains. The surface complementarity between hapten and antibody is sufficient to make the complex specific for only one lactone ring conformation in the hapten. The crystal structure of the 40-50-ouabain complex allows qualitative explanation of the observed fine specificities of 40-50, including that for the binding of haptens substituted at the 16 and 12 positions. Comparison of the crystal structures of 40-50 complexed with ouabain and the previously determined 26-10 anti-digoxin Fab complexed with digoxin, demonstrates that the antibodies bind these structurally related haptens in different orientations, consistent with their different fine specificities. These results demonstrate that the immune system can generate antibodies that provide diverse structural solutions to the binding of even small molecules.

Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Antibody Affinity; Antibody Specificity; Base Sequence; Binding Sites; Cloning, Molecular; Crystallography, X-Ray; Digoxin; Haptens; Hybridomas; Immunoglobulin Fab Fragments; Mice; Models, Molecular; Molecular Sequence Data; Ouabain; Protein Conformation; Sequence Analysis, DNA

Topics: Chromatography, High Pressure Liquid; Digoxigenin; Digoxin; Dosage Forms; Glycosides; Reference Standards

A high-performance thin-layer chromatographic (HPTLC) method for the determination of digoxin and its related compounds digoxigenin bisdigitoxoside (DBD) and gitoxin in digoxin drug substance and tablets was developed. Separation of the three compounds was accomplished on a C18 wettable reversed-phase plate using water-methanol-ethyl acetate (50:48:2, v/v/v) as the mobile phase. The analytes were determined by densitometry using absorbance for digoxin and fluorescence for the two related compounds. All peaks were quantified by peak-height analysis. Linear regression analysis of the data was performed for all three compounds. The calibration range for digoxin was set at 320-480 ng per 5-mm band, equivalent to 80-120% (w/w) of a 400-ng band load, that for DBD was set at 4-12 ng per 5-mm band, equivalent to 1-3% (w/w) of the digoxin load, and that for gitoxin was set at 0.4-1.6 ng per 5-mm band, equivalent to 0.1-0.4% (w/w) of the digoxin load. The limit of quantification (LOQ) for digoxin was 64 ng per 5-mm band with a limit of detection (LOD) of 8 ng per 5-mm band. The LOQs for both DBD and gitoxin were 0.12 ng per 5-mm band with LODs of 0.4 ng per 5-mm band. The linearity range for the digoxin peak height in the absorbance mode was 0-5000 ng per 5-mm band. The linearity range for DBD and gitoxin peak heights in the fluorescence mode was 0-2000 ng per 5-mm band.

Topics: Carbohydrate Sequence; Chromatography, Thin Layer; Digoxigenin; Digoxin; Molecular Sequence Data; Spectrophotometry; Tablets

Two spontaneous variants of the murine anti-digoxin antibody-producing hybridoma cell line 26-10 were isolated by two-color fluorescence-activated cell sorting on the basis of altered hapten binding. The variable region sequences of the antibodies produced by the mutant lines revealed that each contains a single amino acid change in the heavy chain second complementarity determining region. A Tyr to His change at position 50 leads to a 40-fold reduction in affinity for digoxin. A Ser to Phe mutation at position 52 results in a 300-fold reduction in affinity for digoxin. A competition assay involving 33 digoxin analogues was used to examine the specificity of hapten binding of 26-10 and the two mutant antibodies. The position 50 mutant has a distinct specificity change; it exhibits a preference for digoxin congeners containing a hydroxyl group at the steroid 12 position, whereas the 26-10 parent does not. The affinities of all three antibodies for hapten are progressively lowered by substitutions of increasing size at the digoxin steroid D ring 16 position. Although 26-10 binds digoxin and its genin form equally, 12 and 16 steroid position substitutions which lower affinity also confer a preference for a sugar at the steroid 3 position. These results suggest that position 50 contributes to specificity of the antibody and that alterations of the hapten can lead to differences in recognition, possibly through a shift in hapten orientation within the binding site.

Topics: Amino Acid Sequence; Antibodies, Monoclonal; Antibody Specificity; Base Sequence; Digoxigenin; Digoxin; Genes, Immunoglobulin; Haptens; Hybridomas; Immunoglobulin Idiotypes; Models, Molecular; Molecular Sequence Data; Mutation; Ouabain; Structure-Activity Relationship

Positive- and negative-ion mass spectra of five glycoconjugates were obtained using laser desorption/Fourier transform mass spectrometry. These were the glycoalkaloids alpha-solanine and alpha-tomatine and the steroid glycosides gitoxin, lanatoside A and digitonin. Doping with KCl yielded both potassium- and chloride-attachment ions. Few fragment ions were observed for these species, with the exception of digitonin, although the negative-ion spectra showed relatively more fragmentation than the positive-ion spectra. All major fragments appeared to arise from losses of sugar groups due to cleavages at the glycosidic linkages. This contrasted sharply with the behavior of the malto-oligosaccharides studied in this laboratory.

Topics: Alkaloids; Digitonin; Digoxin; Fourier Analysis; Glycosides; Lanatosides; Lasers; Mass Spectrometry; Solanine; Steroids; Tomatine

Topics: Digoxin; Heart Diseases; Humans; Intestinal Absorption

The narrow therapeutic range of cardiac glycosides continually challenges chemists to synthetize new derivatives with improved therapeutic properties. One of the best investigated semi-synthetic glycosides is 16 alpha-gitoxin. Compared to ouabain and gitoxin, it produces positive inotropic effects on the isolated guinea-pig heart in a wider range of concentrations and causes less pronounced rhythmic disturbances. These results were confirmed by electrophysiological investigations in isolated fibres of the canine myocardium and of the Purkinje system, by investigations in the anaesthetized cat and dog and in healthy volunteers. The effects of various semi-synthetic compounds (e.g. actodigin, ASI-222) are described and possibilities to trigger these effects are discussed. Of some significance seem to be differences in the structure of the (Na+ + K+)-ATPase system of different tissues, e.g. the working muscle and the Purkinje system of the heart, as well as differences due to the formation and dissociation of the glycoside-enzyme complex. The significance of K+, Ca2+ and of several pharmacokinetic parameters (e.g. the volume of distribution) for these reactions are briefly discussed.

Topics: Animals; Cardiac Glycosides; Cats; Digoxin; Dogs; Guinea Pigs; Humans; Isomerism; Myocardial Contraction; Ouabain; Purkinje Fibers; Sodium-Potassium-Exchanging ATPase; Stimulation, Chemical; Structure-Activity Relationship; Systole

Hepatic clearance of gitoxin has been studied in the rabbit and compared with that of digoxin using an isolated perfused liver technique. During 1.5 hour perfusions with a modified Krebs-Henseleit solution, gitoxin perfusate levels decreased biexponentially; the distribution and elimination half-lives were estimated to be 0.14 and 1.25 hour, Vd area to be 95.5 ml.g-1 and intrinsic metabolic clearance to be 1.98 ml.min-1.g-1. During 1.5 hour perfusions with modified Krebs-Henseleit solution containing 2.7% bovine serum albumin, gitoxin perfusate levels decreased monoexponentially. This is probably due to protein binding which moderates hepatic uptake so that distribution is not yet complete after 1.5 hour and it is therefore impossible to discriminate the two phases. This was confirmed by 5 hour perfusion experiments with an emulsion of perfluorocarbon in the modified Krebs-Henseleit solution also containing 2.7% bovine serum albumin, during which gitoxin levels decreased biexponentially. Distribution and elimination half-lives have been estimated to be 0.31 and 5.54 hours, Vd area to be 139 ml.g-1 and intrinsic metabolic clearance to be 1.36 ml.min-1.g-1. Gitoxin has been compared in these experimental conditions with digoxin, one of the most often used cardiotonic's. Distribution and elimination half-lives of digoxin were estimated to be 0.34 and 4.52 hours, Vd area to be 46.5 ml.g-1 and intrinsic metabolic clearance to be 0.17 ml.min-1.g-1. Other pharmacokinetic parameters (alpha, beta, V1, V2...) also have been calculated for these three types of perfusion experiments.

Topics: Animals; Bile; Digoxin; In Vitro Techniques; Kinetics; Liver; Male; Perfusion; Protein Binding; Rabbits; Time Factors

Topics: Bile; Digoxin; Humans; Mass Spectrometry

Absorption of 3H-gitoxin and enterohepatic recirculation of the metabolites excreted in the bile were studied in the guinea-pig. Samples were assayed either by RIA or by selective counting of the radioactivity due to tritium. When administered as hydroalcoholic solutions into the stomach or into the duodenum, gitoxin is nearly completely absorbed (94.5%). But the availability of the drug in the systemic circulation is of only 35% (RIA) or 52% (CH2C12-soluble radioactivity). Only 3-5% of the metabolites excreted in the bile enter the enterohepatic cycle.

Topics: Animals; Bile; Digoxin; Female; Guinea Pigs; Intestinal Absorption; Intubation, Gastrointestinal; Kinetics; Liver; Male; Tissue Distribution

Topics: Animals; Biotransformation; Digoxin; In Vitro Techniques; Liver; Rabbits; Time Factors

Recent studies have demonstrated that the biovailability of gitoxin could be increased to 100%. Favorable pharmacokinetic parameters for this glycoside have also been found in humans. The present paper deals with the comparative hemodynamic effect of digoxin and gitoxin on nine patients suffering from heart failure. The study was conducted in a coronary care unit with continuous hemodynamic monitoring. After intravenous administration of 1 mg digoxin or gitoxin, only gitoxin was observed to have an inotropic effect leading to significant improvement of the low cardiac output in these patients.

Topics: Aged; Cardiac Glycosides; Cardiac Output; Digoxin; Female; Heart Failure; Hemodynamics; Humans; Male; Time Factors

Rat and guinea-pig hearts were perfused with gitoxin and gitaloxin at various concentrations. Simultaneously, the amplitude of myocardial contractions was recorded. In the case of guinea-pig, digoxin and digitoxin were studied, too. After perfusion, the amount of cardiac glycoside taken up by each heart was determined. The uptakes of gitoxin and gitaloxin by rat hearts were similar and directly proportional to the glycoside concentration in the perfusion medium. In guinea-pig hearts, the sequence in binding amount of digoxin less than gitaloxin less than gitoxin less than or equal to digitoxin. The positive inotropic effects of the four glycosides in guinea-pig hearts were similar; the toxicity, however, increased in the sequence: gitoxin less than gitaloxin congruent to digoxin less than digitoxin. Briefly, gitoxin is bound to the guinea-pig heart muscle much more than its positional isomer, digoxin; though it shows a similar positive inotropic effect on guinea-pig hearts, gitoxin appears to be markedly less toxic than the three other glycosides.

Topics: Animals; Digitoxin; Digoxin; Extracellular Space; Female; Guinea Pigs; Heart; In Vitro Techniques; Male; Myocardial Contraction; Myocardium; Rats; Species Specificity

The potency of 17 derivatives of 16 alpha-gitoxin was tested in the isolated atrium and heart of the guinea pig and the contractility-increasing activity of the 16 alpha-gitoxin 16 alpha-acetate was compared with that of 16 alpha-gitoxin in the anesthetized dog. The potency of 16 alpha-gitoxin was increased by the substitution of 16 alpha-OH for 16 alpha-methyl ether, 16 alpha-acetate and 16 alpha-nitrate. Substitution of the 16 alpha-acetyl group for substituents with a higher molar volume diminished this enhanced potency. Variation in the digitoxose moiety caused an increase or decrease in potency depending on the position and number of the substituted OH groups. In spite of changes in 16 alpha-OH, the low influence on rhythmicity persisted, as was found in experiments in the dog.

Topics: Acetyldigoxins; Animals; Arrhythmias, Cardiac; Cardiac Glycosides; Digoxin; Dogs; Dose-Response Relationship, Drug; Female; Guinea Pigs; Heart; Heart Rate; Isomerism; Male; Myocardial Contraction; Stimulation, Chemical; Structure-Activity Relationship

Kinetics and metabolism of 3H-gitoxin were determined in the guinea-pig after the i.v. administration of 80 microgram gitoxin/kg. The time course of plasma concentration and urinary amounts remaining to be excreted were described according to the three-compartment linear body model. Apparent half-lives of 4.98 +/- 0.16 hr (plasma) and 24.0 +/- 0.5 hr (urine) were found according to the CH2Cl2-soluble radioactivity. The apparent volume of central compartment and the apparent volume of distribution were estimated with 0.44 +/- 0.05 l/kg and 14.33 +/- 1.131/kg respectively. During 96 hr, approximatively 5.3% of the radioactivity given were eliminated via the kidneys whereas almost 78.7% were recovered in faeces. In animals with bile-duct cannulated, approximatively 82.6% of the dose given were excreted in bile during 6 hr. The hepatic degradation of gitoxin was so fast that almost 70% of the radioactivity recovered in plasma, urine and bile samples after 2 hr could no longer be extracted by dichloromethane. In the lipophilic extracts diginatin and its derivatives were found as possible metabolites of gitoxin. At least four polar metabolites hardly hydrolysable by beta-glucuronidase and by arylsulfatase were detected by TLC in the aqueous extracts from the gastro-intestinal excretions.

Topics: Animals; Bile; Biotransformation; Digestive System; Digitalis Glycosides; Digoxin; Female; Guinea Pigs; Injections, Intravenous; Kinetics; Male; Solubility; Time Factors

The binding of gitoxin, digitoxin and digoxin to human plasma proteins was measured by ultracentrifugation and equilibrium dialysis. At concentrations in the range of therapeutic plasma levels, protein binding amounted, respectively, to 85, 92 and 20%, the last two values being consistent with data reported in the literature. The affinity of purified human albumin was not significantly different for the three cardiac glycosides tested. No other protein than albumin was found to bind gitoxin in human plasma.

Topics: Blood Proteins; Dialysis; Digitoxin; Digoxin; Humans; Isoelectric Focusing; Isomerism; Protein Binding; Ultracentrifugation

The aim of the present investigation was to reevaluate the pharmacokinetic and pharmacodynamic parameters of gitoxin in man. Gitoxin given as a solution is quasi-completely absorbed after oral administration in a fasting man. A dose of 1.5 mg modifies the left ventricular ejection time index (LVETI) as digoxin or digitoxin does. The biological half-life of gitoxin calculated on the basis of plasma concentrations or urinary data is about one day. The urinary elimination of gitoxin is smaller than 21% of the dose. Therefore the two main advantages of gitoxin versus digoxin or digitoxin are: 1) its short biological half-life and 2) its elimination being less dependent on the renal function of the patient.

Topics: Administration, Oral; Adult; Digitalis Glycosides; Digoxin; Female; Half-Life; Humans; Injections, Intravenous; Kidney; Male; Middle Aged

Topics: Animals; Digitoxin; Digoxin; Female; Guinea Pigs; Heart Atria; Isomerism; Kinetics; Male; Myocardial Contraction; Myocardium; Ouabain

Topics: Adolescent; Biomedical Research; Chemistry, Pharmaceutical; Digitalis; Digitalis Glycosides; Digoxin; Geriatrics; Heart Diseases; Pharmacology; Pharmacy; Toxicology

Topics: Biomedical Research; Cardiotonic Agents; Digitalis Glycosides; Digoxin; Diuretics; Drug Therapy; Electrocardiography; Heart Failure; Toxicology

Topics: Arrhythmias, Cardiac; Cardiac Glycosides; Digoxin; Diuretics; Drug Therapy; Heart Failure; Humans; Rubiaceae

Topics: Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Plant Extracts

Topics: Digitalis; Digitalis Glycosides; Digoxin; Humans; Plant Extracts

Topics: Acetyldigitoxins; Digitalis; Digitalis Glycosides; Digoxin; Humans; Plant Extracts

Topics: Digitalis; Digitalis Glycosides; Digoxin; Heart; Heart Diseases

Topics: Digitalis; Digitalis Glycosides; Digoxin; Fluorometry; Plant Extracts

Topics: Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Heart Failure

Topics: Animals; Cats; Digitalis; Digoxin; Dogs; Duodenum; Plant Extracts

Topics: Cardenolides; Chromatography, Paper; Digitalis; Digitalis Glycosides; Digoxin

Topics: Cardiac Glycosides; Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Glycosides; Heart; Humans; Intestines

Topics: Blood; Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Humans; Plant Extracts

Topics: Biological Products; Digoxin; Gliotoxin; Solvents