Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Digitoxin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed2005

High performance liquid chromatographic-mass spectrometric determination of ginsenoside Rg3 and its metabolites in rat plasma using solid-phase extraction for pharmacokinetic studies.

To support pharmacokinetic studies of ginsenosides, a novel method to quantitatively analyze ginsenoside Rg3 (Rg3), its prosapogenin ginsenoside Rh2 (Rh2) and aglycone 20(S)-protopanaxadiol (ppd) in rat plasma was developed and validated. The method was based on gradient separation of ginsenosides present in rat plasma using high performance liquid chromatography (HPLC), followed by detection with electrospray ionization(ESI) mass spectrometry (MS) in negative ion mode with the mobile phase additive, ammonium chloride (500 microM). Differentiation of ginsenosides was achieved through simultaneous detection of the [M(+)Cl(-)] adduct of ginsenoside Rg3 and [M(+)Cl(-)] adducts of its deglycosylated metabolites Rh2 and ppd, and other ions after solid phase extraction (SPE). The /specific ions monitored were m/z 819.50 for Rg3, m/z 657.35 for Rh2, m/z 495.40 for ppd and m/z 799.55 for the internal standard (digitoxin). The mean recoveries for Rg3, Rh2 and ppd were 77.85, 82.65 and 98.33%, respectively using 0.1 ml plasma for extraction. The lower limits of quantification were 10.0, 2.0 and 8.0 ng/ml (equivalent to 0.1, 0.02 and 0.08 ng in each 10 microl injection onto the HPLC column) for Rg3, Rh2 and ppd, respectively. The method has been demonstrated to be highly sensitive and accurate for the determination of Rg3 and its metabolites in rat plasma.

Animals↗
PubMed2006

Studies by biointeraction chromatography of binding by phenytoin metabolites to human serum albumin.

Biointeraction studies based on high performance affinity chromatography were used to investigate the binding of human serum albumin (HSA) to two major phenytoin metabolites: 5-(3-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). This was initially examined by conducting self-competition zonal elution experiments in which m-HPPH or p-HPPH were placed in both the mobile phase and injected sample. It was found that each metabolite had a single major binding site on HSA. Competitive zonal elution experiments using l-tryptophan, warfarin, digitoxin, and cis-clomiphene as site-selective probes indicated that m-HPPH and p-HPPH were interacting with the indole-benzodiazepine site of HSA. The estimated association equilibrium constants for m-HPPH and p-HPPH at this site were 3.2 (+/-1.2)x10(3) and 5.7 (+/-0.7)x10(3)M(-1), respectively, at pH 7.4 and 37 degrees C. Use of these metabolites as competing agents for injections of phenytoin demonstrated that m-HPPH and p-HPPH had direct competition with this drug at the indole-benzodiazepine site. However, the use of phenytoin as a competing agent indicated that this drug had additional negative allosteric interactions on the binding of these metabolites to HSA. These results agreed with previous studies on the binding of phenytoin to HSA and its effects on the interactions of HSA with site-selective probes for the indole-benzodiazepine site.

Allosteric Regulation↗
PubMed1975

Precision of radioimmunoassay with emphasis on curve-fitting procedures.

Direct curve-fitting methods using a digital computer have been employed to analyze the calibration curves of commercial kits for the assay of digoxin, digitoxin, insulin, B12, and renin activity (angiotensin). Inconsistencies have been revealed that suggest some improvements in the commercial kits are desirable. It is not suggested that the use of these kits would yield data of uncertain clinical value, but it is suggested that improvements in consistency would enhance the clinical utility.

Computers↗
PubMed1977

Clinical implications of differences in pharmacodynamic action of polar and nonpolar cardiac glycosides.

The principal effects of cardiac glycosides probably can be classified as parasympathomimetic or sympathomimetic. Data from animals and from man suggest that polar cardiac glycosides, such as ouabain and digoxin, possess greater parasympathomimetic (vagal) cardiac effect for a given amount of sympathomimetic (positive inotropic) cardiac effect than do less polar cardiac glycosides, such as digitoxin. Polar glycosides therefore offer some advantage in uncomplicated paroxysmal atrial tachycardia and in uncomplicated atrial flutter and atrial fibrillation when the principal desired effect is reduction in the number of atrial impulses reaching the ventricles or conversion to normal sinus rhythm. Non-polar glycosides offer an advantage when positive inotropicity is desired but when there is some degree of atrioventricular block or when inappropriate sinus bradycardia or anorexia, nausea, or vomiting are present. Ecotopic impulse formation when due to cardiac glycosides is a toxic manifestation of excessive sympathomimetic effect, but is aggravated by vagal-induced sinus bradycardia, so that both parasympathomimetic and sympathomimetic capability of cardiac glycosides must be considered when dealing with myocardial electrical instability.

Animals↗
PubMed1998

Effects of cardiovascular drugs on ATPase activity of P-glycoprotein in plasma membranes and in purified reconstituted form.

Drug interactions with P-glycoprotein (Pgp) were quantitatively assessed using ATPase assay. Two experimental systems were used, (i) plasma membranes isolated from a multidrug-resistant cell line, which contained 30% Pgp as fraction of total membrane protein, and (ii) purified reconstituted Pgp. The cardioactive drugs verapamil, quinidine, diltiazem, nifedipine, and a series of digitalis analogs, interacted directly with Pgp as shown on ATPase in both systems. Apparent affinities of drug binding were calculated. Direct competition was shown between digitoxin and verapamil. Drug-drug interaction in vivo at the level of Pgp is expected from the results. This approach seems well-suited for empirical determination of drug interactions with Pgp, and prediction of drug-drug interactions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

In vivo digoxin-like immunoreactivity in mice and interference of Chinese medicine Danshen in serum digoxin measurement: elimination of interference by using a chemiluminescent assay.

BACKGROUND: Danshen, a traditional Chinese medicine used in the management of cardiovascular diseases, is available without prescription in the US. Because Danshen is used to treat cardiovascular diseases, we studied the potential interference of Danshen with serum digoxin measurement using various immunoassays. METHODS: Blood was collected 1 day before and then 1 and 2 h after feeding mice with Danshen. The apparent digitoxin activities were measured by the fluorescence polarization immunoassay (FPIA). We also added microliter amounts of Danshen extract to digoxin pools prepared from patients receiving digoxin. The digoxin concentrations were measured using the fluorescence polarization immunoassay (FPIA), microparticle enzyme immunoassay (MEIA) and chemiluminescent assay (CLIA). The observed values were compared with original values. We also fed mice with Danshen. RESULTS: We observed measurable digoxin-like immunoreactivity in sera of mice after feeding with Danshen. We also observed falsely lower digoxin concentrations (negative interference) when MEIA was used for digoxin measurement. However, serum digoxin concentrations were falsely elevated with FPIA. We observed no interference of Danshen in serum digoxin measurement using the CLIA. CONCLUSION: Danshen appears to contain digoxin-like immunoreactivity but does not interfere with serum digoxin measurement when CLIA was used.

Animals↗
PubMed1979

Evaluation of serum digoxin and serum cortisol by radioimmunoassay with the Concept-4.

The solid-phase radioimmunoassay procedures for serum digoxin and cortisol with the Concept-4 were evaluated for specificity, correlation with other radioimmunoassay procedures, parallelism, recovery, carryover, and precision. 1. The detection limits of the digoxin and cortisol assays were 10 pg/tube and 40 pg/tube, respectively. These detections correspond to serum concentrations of 0.25 micrograms/liter and 20 micrograms/liter, respectively, for digoxin and cortisol. 2. Specificity of the digoxin assay was characterized by a 18.3% cross reaction with digitoxin. The anti-cortisol with 11-deoxycortisol, cross reaction with 11-deoxycortisol. 3. The values obtained with the Concept-4 for both procedures demonstrated acceptable correlations with other existing RIA procedures. 4. Dilution studies conducted to determine the parallelism of the 2 assays indicated that both assays demonstrated excellent proportionality between the volume of specimen and the quantity of analyte measured. 5. Analytical recoveries of digoxin and cortisol added to the individual assays average 95% and 101%, respectively. 6. Carryover studies indicated a routine sample-to-sample interaction of less than 0.05% for both assays. 7. The digoxin assay routinely demonstrated intra- and inter-assay variations of less than 7.4% and less than 10.0%, respectively. The precision data for cortisol indicated intra- and inter-assay variations of less than 6.7% and less than 9.1%, respectively.

Chemistry, Clinical↗
PubMed2001

Effect of P-glycoprotein modulators on the human extraneuronal monoamine transporter.

The aim of this work was to investigate the effect of P-glycoprotein modulators on human extraneuronal monoamine transporter (EMT)-mediated transport. The experiments were performed using a cell line from human embryonic kidney (HEK293 cells) stably transfected with pcDNA3hEMT (293(hEMT)), or with pcDNA3 alone (293(control)). Of the P-glycoprotein modulators tested, rhodamine123, verapamil and daunomycin concentration-dependently inhibited EMT-mediated uptake of [3H]1-methyl-4-phenylpyridinium ([3H]MPP(+)). The corresponding IC(50)'s were found to be 3.6, 37 and 130 microM, respectively. By contrast, vinblastine, digitoxin and cyclosporine A were devoid of effect. The endogenous organic cation tyramine, but not choline, inhibited EMT-mediated transport (IC(50) of 468 microM). Moreover, L-arginine and L-histidine (up to 1 mM) did not affect [3H]MPP(+) uptake. Finally, MPP(+) and tyramine trans-stimulated [3H]MPP(+) uptake, but rhodamine123 had no effect, and verapamil and daunomycin trans-inhibited [3H]MPP(+) uptake. In conclusion, this study shows that several cationic modulators of P-glycoprotein inhibit EMT-mediated transport. As a consequence, the interaction of P-glycoprotein modulators with EMT must be taken into account, and the consequences of this interaction must not be forgotten when using such drugs in vivo.

1-Methyl-4-phenylpyridinium↗
PubMed1998

Properties of ginseng saponin inhibition of catecholamine secretion in bovine adrenal chromaffin cells.

To investigate the relationship between the inhibitory effects of ginseng saponins (ginsenosides) on acetylcholine-evoked secretion of catecholamines and the structures of ginsenosides, we examined the effects of ginsenoside-Rg3 and -Rh2, which are panaxadiol saponins, 20(R)- and 20(S)-ginsenoside-Rg2, which are epimers involving the hydroxyl group at C-20 of sapogenin, and other plant saponins on the acetylcholine-evoked secretion of catecholamines from cultured bovine adrenal chromaffin cells. The ginsenoside-Rg3 (1-100 microM) and -Rh2 (10-100 microM) greatly reduced the acetylcholine-evoked secretion in a concentration-dependent manner comparable to that of ginsenoside-Rg2, a panaxatriol saponin, which was the most potent inhibitor in our previous study. 20(R)- and 20(S)-ginsenoside-Rg2 (1-100 microM) similarly reduced the acetylcholine-evoked secretion. In contrast, saikosaponin-a, glycyrrhizin and the cardiac glycosides (100 nM-100 microM), digitoxin and digoxin, had no significant inhibitory effect on catecholamine secretion. Saikosaponin-c (10-100 microM), however, had an inhibitory effect, which was less than that of ginsenoside-Rg2 and -Rg3. These results strongly suggest that the inhibitory effects of ginsenosides on the acetylcholine-evoked secretion of catecholamines from bovine adrenal chromaffin cells are a unique property of ginseng. Further, the relationship between the inhibitory effects and the structures of ginsenosides is discussed.

Animals↗
PubMed1979

Gas-liquid chromatography of digitoxigenin and digoxigenin as acetates of their epoxygeninic acid methyl esters.

Gas chromatographic analysis of ditigoxigenin and digoxigenin, the genins of the cardenolide glycosides digitoxin and digoxin, cannot be done without derivatization. However, during the derivatization, side-reactions often present serious problems. A procedure has been found for transforming digitoxigenin and digoxigenin into the corresponding acetates of their epoxygeninic acid methyl esters, which are stable compounds and suitable for gas chromatographic analysis.

Acetates↗
PubMed1989

High-performance liquid chromatographic determination of secondary cardiac glycosides in Digitalis purpurea leaves.

An analytical method for the determination of secondary cardiac glycosides in Digitalis purpurea leaves by high-performance liquid chromatography (HPLC) is described. The procedure consisted of extraction of dry leaf powder with ethanol-chloroform (2:1) and clean-up by Sep-Pak cartridges prior to HPLC analysis. HPLC was performed on an octylsilyl bonded silica column, using acetonitrile-methanol-water (4:4:5) for trisdigitoxosides and acetonitrile-methanol-water (8:30:43) for strospeside; the effluent was monitored by ultraviolet detection (at 220 nm). Quantitation of these cardiac glycosides was carried out by the internal standard method. The amounts of digitoxin, gitoxin, gitaloxin and strospeside per 100 mg of dry leaf powder were estimated to be 22.6, 14.0, 54.7 and 1.9 micrograms, respectively. The method is sufficiently sensitive and reproducible to assay secondary glycosides in Digitalis purpurea leaves.

Chemical Phenomena↗
PubMed1985

Diffusion-controlled receptor occupancy determines the rate of inotropic action of some cardioactive steroids.

In guinea-pig myocardium the rates of onset and offset of the inotropic effects of digitoxigenin-monodigitoxoside, digitoxin, ouabain, digoxin, digoxigenin, and dihydroouabain correlated negatively, and independently of the lipophilicity of the steroids, with their intropic and Na-K-ATPase inhibitory potencies. The intropic potency of ouabain was considerably higher than that of dihydroouabain whereas its inotropic effect developed much more slowly (T50 17 min v. 3 min). By contrast, the inhibition of sarcolemmal Na-K-ATPase by equieffective concentrations of these steroids appeared at similar rates within a few minutes. The homogeneity of the effects, as shown by parallel concentration-effect curves with similar order of potencies of the inotropic and the Na-K-ATPase inhibitory effects, excluded the different activation of inhomogeneous receptor populations. The correlation between the geometry of the papillary muscles and the rates of onset of the inotropic ouabain effect or tissue/medium ratios of 3H-ouabain indicated the relevance of diffusion. The discrepancy between the rates of action in sarcolemmal preparations and in papillary muscles could thus be related to the different diffusion distances. The apparently contradictory results in which receptor occupation (dependence of T50 on EC50) appeared as the rate-limiting step are explained by diffusion-controlled receptor occupancy: the reduced rate of diffusion due to an affinity-dependent reduction of the free drug concentration (receptor occupancy as a temporal 'site of loss') accounted for the slow onset of the inotropic effect of the highly potent cardioactive steroids.

Animals↗
PubMed2000

Selective inhibition of human erythrocyte Na+/K+ ATPase by cardiac glycosides and by a mammalian digitalis like factor.

Na+/K+ATPase is a transport membrane protein which contains the functional receptor for digitalis compounds. In this work we compare the inhibition curves of Na+/K+ATPase measured by the inhibition of 86Rb uptake in human red blood cells by cardiac glycosides and by an endogenous digitalis like factor (EDLF) extracted from human newborn cord blood. The curves of Na+/K+TPase inhibition show a monophasic shape for ouabain, strophantidin, digitoxin, proscillaridin and EDLF whereas a biphasic shape for ouabagenin, digoxin, digoxigenin and digitoxigenin. All the drugs are potent inhibitors of erythrocyte Na+/K+ATPase with an IC50 ranging from 1.8 x 10(-9) M to 1.4 x 10(-11) M for the higher affinity binding site and from 1.8 x 10(-6) M to 5.5 x 10(-9) M for the lower affinity site. Digitoxigenin is the most active showing the higher active site at 1.4 x 10(-11) M. Ouabain and digoxin have higher affinity compared with their corresponding genins, while digitoxigenin shows a binding site with higher affinity than the respective cardiac glycosides. The increased affinity of the drugs to Na+/K+ATPase may be related to a lipophilic region in correspondence of the carbons 10, 9, 11, 12, 13 of the steroid nucleus, situated in the opposite side with respect of the C-OH-14. The comparison of the inhibition curves and the HPLC profile of newborn EDLF and of the investigated cardenolides suggest that EDLF may be a compound identical or very similar to ouabain.

Cardiac Glycosides↗
PubMed2001

Determination of bufalin-like immunoreactivity in serum of humans and rats by time-resolved fluoroimmunoassay for using a monoclonal antibody.

The existence of a mammalian natriuretic substance or endogenous digitalis-like factor, which inhibits Na+,K+-ATPase and thereby regulates body fluid volume, has been speculated for a long time but has yet to be defined. We established in the present study a simple and highly sensitive procedure to measure bufalin, a constituent of toad venom preparation and a specific inhibitor of Na+,K+-ATPase by time-resolved fluoroimmunoassay (TR-FIA) and using a monoclonal antibody. The antibody was specific to bufalin and resembled bufadienolides but showed no cross-reactivity with digitoxin and ouabain. A bufalin-like immunoreactivity was detectable in serum of humans and rats by the proposed TR-FIA. The levels of bufalin-like immunoreactivity in serum of healthy volunteers were significantly correlated with their systolic blood pressure. Moreover, bufalin-like immunoreactivity in serum of Dahl-S rats increased in parallel with a period of high-salt diet. These results suggest that increased bufalin-like immunoreactivity may be associated with certain types of hypertension.

Animals↗
PubMed2002

Enhancement of radiotherapy by oleandrin is a caspase-3 dependent process.

Cardiac glycosides such as digitoxin and ouabain have previously been shown to be selectively cytotoxic to tumor as opposed to normal cells. Moreover, this class of agents has also been shown to act as potent radiosensitizers. In the present study we explored the relative radiosensitization potential of oleandrin, a cardiac glycoside contained within the plant extract known as Anvirzel that recently underwent a Phase I trial as a novel drug for anticancer therapy. The data show that oleandrin produces an enhancement of sensitivity of PC-3 human prostate cells to radiation; at a cell survival of 0.1, the enhancement factor was 1.32. The magnitude of radiosensitization depended on duration of exposure of cells to drug prior to radiation treatment. While a radiosensitizing effect of oleandrin was evident with only 1h of cell exposure to drug, the effect greatly increased with 24h oleandrin pretreatment. Susceptibility of PC-3 cells to oleandrin and radiation-induced apoptosis was dependent on activation of caspase-3. Activation was greatest when cells were exposed simultaneously to oleandrin and radiation. Inhibition of caspase-3 activation with Z-DEVD-FMK abrogated the oleandrin-induced enhancement of radiation response suggesting that both oleandrin and radiation share a caspase-3 dependent mechanism of apoptosis in the PC-3 cell line.

Adenocarcinoma↗
PubMed2002

Digitalis; impinges on more than just the (ion-) pump.

Some forms of digitalis, such as digitoxin, inhibits proliferation and induces apoptosis in cancer cells in clinically relevant concentrations. Recently, it has been demonstrated that digitalis, in addition to inhibiting the Na(+)/K(+)-ATPase, also signals through the pathways of the epidermal growth factor receptor (EGFR). Digitalis has complex dose-dependent mechanisms of action involving many signaling systems and the relevance of this for the anticancer effects are discussed.

Antineoplastic Agents↗
PubMed1986

Digoxin and metabolites in urine and feces: a fluorescence derivatization--high-performance liquid chromatographic technique.

A high-performance liquid chromatography method is described for the determination of digoxin and its metabolites digoxigenin, digoxigenin monodigitoxoside, digoxigenin bis-digitoxoside and dihydrodigoxin (20S and 20R) excreted in urine and feces. The urine sample or fecal supernatant is extracted with methylene chloride in the presence of digitoxigenin or digitoxin as internal standard. Pre-column derivatization is achieved using 1-naphthoyl chloride with subsequent separation of the derivatized compounds on either a normal- or reversed-phase system with fluorescence detection. Recoveries for digoxin and all metabolites from fecal samples were in the range 60-74%, which is comparable to that previously determined for urine samples. Standard curve data revealed linearity over a wide range of concentrations. Coefficients of variation for the analysis were less than 10% for all compounds over a range of 5-125 ng per ml urine and 10-250 ng per 200 mg feces. Peaks for digoxin and metabolites in urine and feces were obtained when human excreta were analyzed.

Chromatography, High Pressure Liquid↗