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Biomedical subjects

M Lesne

Publications and source records attributed to M Lesne.

At least 37 records · Page 2Linked to original sources
PubMed1982

Studies on the pharmacokinetics and the metabolism of gitoxin in the guinea-pig: II. the enteral absorption and the enterohepatic recirculation.

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.

Animals↗
PubMed1981

Automated particle-counting immunoassay for digoxin.

We describe a non-radioisotopic automated immunoassay for serum digoxin in the therapeutic range at 50 samples per hour by use of the particle-counting immunoassay technique and a special reagent, rheumatoid factor. Digoxin is determined by evaluating its inhibitory activity on the agglutination of digoxin-coated latex particles. The agglutinating system consists of the anti-digoxin IgG mixed with rheumatoid factor. This anti-IgG autoantibody reacts with IgG when they are aggregated or bound to a surface. Interference by serum proteins was prevented by pepsin digestion at 37 degrees C. Correlation with radioimmunoassay was r = 0.94 for 109 samples with concentrations between 0 and 5.7 micrograms/L. Analytical recovery overall averaged 102%. Within-assay precision (CV) ranged from 12.5% at 0.96 micrograms/L to 4.4% at 2.97 micrograms/L; between-assay precision varied from 8.4% at 0.75 micrograms/L to 5.8% at 2.92 micrograms/L.

Antigen-Antibody Complex↗
PubMed1981

Cardiac glycosides and their metabolites levels in plasma and heart of guinea-pigs after I. V. administration.

One hr, 3 hr and 6 hr after i.v. injection of tritiated gitoxin, digoxin and digitoxin to the guinea-pig, the chloroform-insoluble metabolites, mainly conjugates known to be cardio-inactive, represent two thirds of the cardiac glycoside and metabolites content of plasma for gitoxin, half for digitoxin and one quarter for digoxin. Most of the compounds taken up by the myocardium are chloroform-soluble and may be considered as cardio-active. Considering the nature and proportions of the unchanged cardiac glycoside and its cardio-active metabolites in the myocardium of the guinea-pig, the cardiac effects that would be measured after administration of digoxin ar due to unchanged digoxin only; after administration of digitoxin, these effects are partly due to unchanged digitoxin but also to 12 beta-hydroxylated metabolites; after administration of gitoxin, besides unchanged gitoxin, the hydrolysis products of the sugar chain of gitoxin may contribute to the cardiac effects. The data obtained in plasma and in myocardium between 1 and 6 hr after administration of digoxin or gitoxin show that the distribution of the unchanged cardiac glycoside and each chloroform-soluble metabolite, from plasma to myocardium, is achieved 1 hr after administration. This situation does not occur with digitoxin and its metabolites.

Animals↗
PubMed1981

Contrasting effect on cardiac output of digoxin and gitoxin in humans during congestive heart failure.

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.

Aged↗
PubMed1980

Uptake and pharmacological effect of gitoxin and gitaloxin in rat and guinea-pig perfused hearts. Comparison with digitoxin and digoxin.

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.

Animals↗
PubMed1980

Studies on the pharmacokinetics and the metabolism of gitoxin in the guinea-pig: I. Disposition kinetics following an i.v. bolus of 3H-gitoxin.

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.

Animals↗
PubMed1979

The binding of gitoxin to human plasma proteins.

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.

Blood Proteins↗
PubMed1979

Digoxin acute intoxication: evaluation of the efficiency of charcoal hemoperfusion.

Since there is no widely used method of reducing the severity of massive digoxin intoxication, the capacity of hemoperfusion with coated, activated charcoal to remove digoxin was evaluated in a case of suicidal digoxin ingestion (25 mg). Seven hours after ingestion the digoxin plasma level was equal to 8.9 ng/ml. This was decreased to 4.5 ng/ml after 6 hr hemoperfusion. The amount of digoxin adsorbed by the column represents 4.8% of the absorbed dose. At a blood flow rate of 170 ml/min, the mean digoxin clearance by hemoperfusion was 44.5 +/- 26.9 ml/min. From these results we conclude that charcoal hemoperfusion in acute digoxin intoxication is of little value.

Adult↗
PubMed1979

Bioavailability study of gitoxin in a solid dosage form.

Although the cardiotonic activity of gitoxin is known for almost half a century, this digitalis glycoside has never been used in therapy, due to its apparent lack of resorption after administration by oral route. Recent studies have demonstrated that the bioavailability of gitoxin could be upraised to 100% provided it be given as a hydroalcoholic solution. The present paper deals with the development of a solid dosage form (tablets) using a physical association of gitoxin and sodium escinate.

Adult↗