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At least 19 recordsLinked to original sources
PubMed1978

The bioavailability of alpha-acetyldigoxin from Card-Hydergin--a fixed combination of Hydergine and acetyldigoxin.

In six healthy volunteers the bioavailability of alpha-acetyldigoxin in solution and tablet form was compared with a tablet which in addition to alpha-acetyldigoxin contained the DH-ergot alkaloid Hydergine in identical galenic formulation. After a single dose, bioavailability was measured from the areas under the plasma level time curves and from the cumulative amount of digoxin excreted into the urine. The addition of Hydergine did not change the plasma level/time profile and the bioavailability of alpha-acetyldigoxin. When this parameter was compared to the solution, a relative bioavailability of approximately 80% could be calculated for both tablets. Relating this data to a previously published infusion experiment, their absolute bioavailabilities amounted to about 70%.

Adult↗
PubMed1977

[Isomerisation and bioavailability of beta- and alpha-acetyldigoxin (author's transl)].

Bioavailability of acetylated derivatives of digoxin tablets have been studied in healthy subjects after a single oral and intravenous dose as well as during maintenance therapy. alpha-acetyldigoxin shows a lower bioavailability than beta-acetyldigoxin even if the alpha-acetylated derivative is incorporated in a matrix of aerosil (SiO2). Moreover, beta-acetyldigoxin can be transferred to alpha-acetyldigoxin in alkaline solutions. This isomerisation leads to a decrease of the bioavailability of such fixed preparations which contain beta-acetyldigoxin and the hygroscopic salts of potassium-magnesium-aspartate. A prevention of the isomerisation is attained by isolating beta-acetyldigoxin from potassium-magnesium-aspartate. The bioavailability of a such new formulation is comparable to that of beta-acetyldigoxin alone. The experiments show the bioavailability of acetylated derivatives of digoxin to be influenced by the physico-chemical properties of a drug and its preparation.

Acetylation↗
PubMed1975

[Bioavailability of beta-acetyldigoxin and digoxin (author's transl)].

Five beta-acetyldigoxin and two digoxin preparations were given orally to eleven healthy volunteers. In a single dose crossover study bioavailability of the oral preparations was compared to an intravenous injection of digoxin as a standard for complete bioavailability. A mean bioavailability of 82% (sx = 1.8) was found for beta-acetyldigoxin tablets (Novodigal¿), PETN/beta-acetyldigoxin tablets (Nitro-Novodigal¿), oxyfedrin/beta-acetyldigoxin tablets (ildamen¿-Novodigal¿) and beta-acetyldigoxin liquid. Analysis of variance shows no differences in absorption for the five tested beta-acetyldigoxin preparations. Beta-Acetyldigoxin administered orally in an alcoholic solution is nearly completely absorbed (94%) whereas a corresponding digoxin solution is available to a significantly lesser content (79.2%). Comparable differences in absorption were found for beta-acetyldigoxin tablets (81%) and digoxin tablets (Digacin¿) (63.5%).

Administration, Oral↗
PubMed2001

P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin.

Digoxin is a drug with a narrow therapeutic index, which is substrate of the ATP-dependent efflux pump P-glycoprotein. Increased or decreased digoxin plasma concentrations occur in humans due to inhibition or induction of this drug transporter in organs with excretory function such as small intestine, liver and kidneys. Whereas particle size, dissolution rate and lipophilic properties have been identified as determinants for absorption of digitalis glycosides, little is known about P-glycoprotein transport characteristics of digitalis glycosides such as digitoxin, alpha-methyldigoxin, beta-acetyldigoxin and ouabain. Using polarized P-glycoprotein-expressing cell lines we therefore studied whether these compounds are substrates of P-glycoprotein. Polarized transport of digitalis glycosides was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells (LLC-PK1 cells stably transfected with the human MDR1 P-glycoprotein). Inhibition of P-glycoprotein-mediated transport of these compounds in Caco-2 cells was determined using the cyclosporine analogue PSC-833 (valspodar) as inhibitor of P-glycoprotein. No polarized transport was observed for ouabain. However, basal-to-apical transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin was greater than apical-to-basal transport in Caco-2 and L-MDR1 cells. In Caco-2 cells net transport rates of these compounds were similar to those of digoxin (digoxin: 16.0+/-4.4%, digitoxin: 15.0+/-3.3%, beta-acetyldigoxin: 16.2+/-1.6%, alpha-methyldigoxin: 13.5+/-4.8%). Furthermore, polarized transport of these compounds could be completely inhibited by 1 microM PSC-833. In summary, these data provide evidence that not only digoxin, but also digitoxin, alpha-methyldigoxin and beta-acetyldigoxin are substrates of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1977

[Fate of orally administered beta-acetyldigoxin in man (author's transl)].

After oral administration of 3H-beta-acetyldigoxin to four patients aspirates of gastric and duodenal contents were obtained with intestinal tubes. Concentration of label in the aspirates was measured. Radiochromatographic analysis of the aspirates showed that 90% of the beta-acetyldigoxin was unchanged during the period it was in the stomach. In the duodenum a small part of the administered dose was transformed to 3H-alpha-acetyldigoxin. When given 3H-beta acetyl-digoxin intraduodenally to three subjects in the portal vein blood 93% of the labelled compunds was 3H-digoxin. According to these data the absorption of beta-acetyldigoxin can be described as follows: After oral ingestion beta-acetyl-digoxin rapidly passes the stomach with a half-life of 10 min. Most of the glycoside is absorbed unchanged in the duodenum. On passage through the intestinal wall the acetyl group is removed and digoxin is the active drug reaching the heart.

Administration, Oral↗
PubMed1991

High-performance liquid chromatographic determination of alpha-acetyldigoxin in Digitalis lanata leaves.

An analytical method for the determination of alpha-acetyldigoxin in Digitalis lanata leaves by HPLC has been developed. The procedure consists of extraction of dry leaf powder with 50% methanol and cleanup by a Sep-Pak C18 cartridge prior to HPLC analysis. The quantitation is carried out by the incorporation of beta-methyldigoxin as an internal standard. HPLC is performed on an octylsilyl bonded silica column with acetonitrile/methanol/water (100/11/188, v/v). The effluent is monitored by uv absorption at 220 nm. The amount of alpha-acetyldigoxin per 100 mg of dry leaf powder is estimated at 5.55 +/- 0.21 micrograms (mean +/- SD). The average recovery of alpha-acetyldigoxin from added samples is 97.2%. The present method is sensitive, reliable, and relatively simple. Application of this HPLC method to the analysis of samples obtained by fermentation of the leaf powder is also demonstrated.

Acetyldigoxins↗
PubMed1979

[Biological availability of digoxin and beta-acetyldigoxin after single-dose administration (author's transl)].

The biological availability of digoxin tablets (Lanicor) and beta-acetyldigoxin tablets (Novodigal) was tested after single-dose administration. Plasma levels over 48 hours, the area under the blood-level curves and the cumulative urinary excretion over seven days served as a measure of biological availability. The area under the blood-level curve after 1.0 mg digoxin by mouth was 40.7 +/- 1.7 ng . ml-1 . h and after 1.0 mg beta-acetyldigoxin by mouth 39.1 +/- 1.4 ng . ml-1 h, compared with 56.1 +/- 1.4 after 1.0 mg digoxin intravenously. Seven days later 0.67 +/- 0.12 mg digoxin of the orally administered digoxin, 0.68 +/- 0.12 mg digoxin of the orally administered beta-acetyldigoxin and 0.81 +/- 0.08 mg of the intravenously administered digoxin were excreted in the urine. There was no significant difference in the biological availability of the two drugs (P greater than 0.05).

Acetyldigoxins↗
PubMed1992

[Absolute bioavailability of beta-acetyldigoxin from tablets and drops in healthy subjects].

In a crossover design in random order 12 healthy male volunteers were given either beta-acetyldigoxin (Novodigal, CAS 5511-98-8) tablets, oral solution or i.v. application at a digoxin equivalent dose of 0.284 mg. To reach steady state each preparation was given for 10 days on a once-daily schedule. On days 8, 9 and 10 of each observation period blood was sampled to determine trough concentrations of digoxin in steady state. In addition, on day 10 blood was collected repeatedly at appropriate time intervals and urine was sampled concomitantly for 24 h. Trough values during steady state and 24 h AUC were used to calculate digoxin bioavailability for tablets and oral solution. From trough values, the mean bioavailability for beta-acetyldigoxin tablets was 91.2% (range 73.1-118.1) and for solution 93.8% (range 65.7-114.8). Using the AUCs 0-24 h at steady state bioavailability was calculated 77.7% for the tablets and 84.5% for the solution. Since trough values in steady state represent the body burden of digoxin which is supposed responsible for the therapeutic effect, trough values should be given priority for the determination of digoxin bioavailability from beta-acetyldigoxin tablets and solution. All formulations were well tolerated. No clinically relevant side effects were observed.

Acetyldigoxins↗
PubMed1992

[Differences in mechanisms of action of beta-acetyldigoxin, strophanthin K and ouabain].

In vitro on skinned myocardial fibers (SMF) with extracted or functionally inactivated enzymes and membranes of mitochondria, longitudinal sarcoplasmic reticulum, triads and sarcolemma, new evidence of beta-acetyldigoxin and strophanthin K direct stimulating effects on contractile protein system of myocardium has been obtained. It has been revealed in energy release stimulation and force generation, in quantitative (beta-acetyldigoxin) or quantitative and qualitative (strophanthin K) stimulation of energy transduction, in the increase of contractile process cooperativity and Ca-sensitivity of SMF as well as in the SMF relaxation time extension (in the case of strophanthin K). It is suggested that different effects of beta-acetyldigoxin and strophanthin K are due to the differences in the conformations of actomyosin ensembles formed by strong bound (AMESB), which are induced by the influence of these cardiac glycosides. It has been demonstrated that ouabain (strophanthin K) has no direct effect on functioning of AMESB.

Acetyldigoxins↗
PubMed1991

[Effects of strophanthin K and beta-acetyldigoxin in vitro on energy transformation of myocardial contractile protein system in toxic-allergic lesions of the cardiac muscle].

Strophanthin K and beta-acetyldigoxin in vitro in concentration of 10(-6) M in TAM sharply increased the force generated by isolated myocardial contractile protein system (MCPS), and normalized the work performed by the system. This was accompanied by increase of ATP internal energy release (enthalpy) intensity, while a portion of energy, dissipating into heat did not increase proportionally. The mechanical efficiency of contractile process was normalized due to beta-acetyldigoxin, and exceeded the normal level due to strophanthin K effect. Strophanthin K proved a positive effect on quantitative and qualitative economy of MCPS energy utilization, while beta-acetyldigoxin effected, on the whole, extensively.

Acetyldigoxins↗
PubMed1984

Changes in metildigoxin pharmacokinetics in cirrhosis of the liver: a comparison with beta-acetyldigoxin.

In a prospective randomized study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy volunteers were treated daily with either 0.3 mg metildigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In patients receiving metildigoxin therapy the ratio of beta-methyldigoxin/digoxin in the serum was determined by HPLC. The digoxin levels in patients with cirrhosis treated with metildigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. The higher total serum-digoxin levels in patients with cirrhosis of the liver after moderate saturation with metildigoxin are caused by reduced demethylation of beta-methyldigoxin to digoxin due to impaired liver function. A comparison with healthy volunteers showed that the reduced hepatic metabolism in the cirrhotic patients caused changes in the pharmacokinetics: a reduced metildigoxin clearance and a smaller distribution volume were found. According to our findings there is more danger of digitalis toxicity in patients with cirrhosis of the liver on a standard dosage of metildigoxin than on a standard dosage of beta-acetyldigoxin.

Acetyldigoxins↗
PubMed1981

Digoxin concentration in cerebrospinal fluid-a study carried out after 9 days of treatment of beta-methyldigoxin or beta-acetyldigoxin.

Two groups of seven healthy volunteers were treated for 9 days with either 0.3 mg beta-methyldigoxin or 0.4 mg beta-acetyldigoxin daily, applied orally. On the 10th day, digoxin concentrations in plasma and cerebrospinal fluid (CSF) were determined by radioimmunoassay. After therapy with beta-methyldigoxin the plasma/CSF digoxin concentration ratio was 3.7:1; after therapy with beta-acetyldigoxin it was 3.2:1. There was no significant difference in the plasma/CSF digoxin concentration ratio after 9 days of treatment with equipotent doses of beta-methyldigoxin and beta-acetyldigoxin.

Acetyldigoxins↗
PubMed1981

[Pharmacokinetics of beta-methyldigoxin and beta-acetyldigoxin in patients with cirrhosis of the liver (author's transl)].

In this prospective randomised study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy male volunteers were treated with either 0.3 mg beta-methyldigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) daily, orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In subjects receiving beta-methyldigoxin therapy the ratio of beta-methyldigoxin to digoxin in the serum was determined by liquid chromatography. The digoxin levels in patients with cirrhosis treated with beta-methyldigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. Alterations in pharmacokinetics may cause the higher total serum digoxin concentrations in cirrhotic patients. The following factors seem to be important: longer elimination half life, changes in distribution volume and reduced renal clearance. There is greater danger of digitalis toxicity in patients with cirrhosis of the liver on standard dosage of beta-methyldigoxin than on standard dosage of beta-acetyldigoxin.

Acetyldigoxins↗
PubMed1977

The bio-availability of beta-acetyldigoxine (Novodigal) alone and combined with oxyfedrine (Ildamen-Novodigal).

The bio-availability of various galenic preparations of beta-acetyldigoxine was tested in six healthy probands after a single oral dose (1 mg). The availability parameters were calculated from the areas under the plasma concentration curves and from the cumulative urinal excretion. There was no significant difference between the bio-availabilities of Novodigal (beta-acetyledigoxine tablets), Ildamen-Novodigal (beta-acetyldigoxine and oxyfedrine) and an alcoholic solution of beta-acetyldigoxine. Correlation calculations showed that the determination of the plasma concentration courses up to six hours after substance application are most favourite in regard to judging the absorption processes of digoxine preparations. For the assessment of the bio-availability, the methods of comparing the areas under the blood level curves of 0 to 6 hrs and of comparing the cumulative urinal excretion over a period of 24 hrs were of equal validity.

Adult↗
PubMed1977

The bio-availability of beta-acetyldigoxine alone and combined with aluminum hydroxide and magnesium hydroxide (Alucol).

The bio-availability of Novodigal (beta-acetyldigoxine) alone and applied together with Alucol (aluminum hydroxide, magnesium hydroxide) was studied in six healthy probands. Bio-availability parameters were calculated from the areas under the plasma concentration curves and from the comparison of the blood levels after absorption during steady state. There was no significant difference between the bio-availability of beta-acetyldigoxine alone and that of the combination with Alucol. Thus, beta-acetyldigoxine combined with antacids of the aluminum hydroxide and magnesium hydroxide type can be applied in the same dosage as usual since no decrease of effect has to be apprehended.

Adult↗
PubMed1994

Photostability studies of ouabain, alpha-acetyldigoxin and digoxin in solid state.

Ouabain, alpha-acetyldigoxin and digoxin were subjected to irradiation using different light sources in crystalline state and their respective yields of photoproducts were determined densitometrically. alpha-Acetyldigoxin was found to be less stable than digoxin yielding a higher percentage of photoproducts under each light source examined. Ouabain showed photostability under the conditions of investigation.

Acetyldigoxins↗
PubMed1981

Effects of cytostatic drugs on plasma level and renal excretion of beta-acetyldigoxin.

Mucosal defects decrease digoxin absorption in patients with malabsorption syndromes. Since the intestinal mucosa can be damaged by cytostatic drugs, we investigated their effects on digoxin plasma levels and urinary digoxin excretion. In six patients with malignant lymphoma who received 0.8 mg beta-acetyldigoxin before and 24 hr after treatment with a combination of cyclophosphamide, oncovin, procarbazine, and prednisone (COPP) or cyclophosphamide, oncovin, and prednisone (COP), plasma digoxin concentrations were measured 0 to 8 hr after the dose and areas under the plasma concentration-time curves were calculated. In 15 patients on 0.3 mg of beta-acetyldigoxin daily, plasma glycoside concentrations and renal excretion were measured daily before and after COPP, COP, cyclophosphamide, oncovin, cytosine-arabinosine, and prednisone (COAP), or adriamycin, bleomycin, and prednisone (ABP) treatment schemes. The diminished steady-state glycoside plasma concentrations and daily renal glycoside excretion during the 24 to 168 hr after the cytostatic drug established reversible impairment of digoxin absorption. The delayed time to peak after a single dose of digoxin during cytostatic drug therapy shows that extent and rate of digoxin absorption are reduced. To maintain adequate control of digoxin therapy in patients treated with cytostatic drugs, plasma levels should be monitored.

Acetyldigoxins↗