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Biomedical subjects

N Rietbrock

Publications and source records attributed to N Rietbrock.

At least 127 records · Page 7Linked to original sources
PubMed1979

[Comparative study of the absolute bioavailability of four oral digoxin preparations (author's transl)].

In a randomized cross over study on 19 normal subjects the absolute bioavailability of four oral digoxin preparations (Digacin containing a silica gel matrix as preparation A and three other commercial digoxin tablet preparations, B, C and D) were investigated applying digoxin in a daily dose of 0.25 mg for 10 consecutive days. On day 8, 9 and 10, the serum digoxin concentration and the amount of digoxin excreted with 24-h urine were measured radioimmunologically. After i.v. administration the mean serum digoxin concentration amounted to 0.58 ng/ml. With oral administration preparation A achieved the highest concentration (0.51 ng/ml) and preparation C the lowest (0.42 ng/ml). Accordingly, after i.v. administration 118 microgram digoxin were excreted with the 24-h urine and 95 microgram after the oral preparation A and 73 microgram after preparation C, respectively. From the serum concentrations and the amount excreted with the urine the absolute bioavailability was calculated: 88.0 and 80.4%, respectively, for preparation A, 82.5 and 67.2% for preparation B, 72.7 and 61.8% for preparation C, 76.2 and 67.3% for preparation D.

Administration, Oral↗
PubMed1978

[Suicide with beta-methyldigoxin (author's transl)].

A 50-year-old woman committed suicide by taking an overdose of beta-methyldigoxin. The interval between swallowing the tablets and death was about 60 minutes. Plasma and tissue samples, taken 163 hours after death, were analysed for glycosides by radioimmunoassay. The plasma-glycoside level was 75.1 ng/ml, in the left ventricular myocardium it was 143.2 ng/g wet-weight. and in the right ventricular myocardium 159.7 ng/g wet-weight. The tissue-plasma ratio for the various parts of the heart varied from 0.8 to 2.1. Death occurred in the early distribution stage.

Digoxin↗
PubMed1978

[Pharmacokinetics of digoxin and methyldigoxin in patients with acute hepatitis (author's transl)].

After i.v. application of 3h-digoxin or 3H-methyldigoxin to 5 healthy volunteers and 5 patients with acute hepatitis, respectively (0.75 mg daily for 3 days and 0.375 for the following 2 days) total radioactivity in urine and plasma were determined. Chloroform-soluble and -insoluble glycosides were separated and the chloroform-soluble fraction was determined by TLC. 3 days after methyldigoxin application plasma levels reached toxic values in the patient group (2.73 +/- 0.48 ng/ml), whereas in patients receiving digoxin a mean plasma level of 0.91 +/- 0.21 ng/ml was obtained. During the first 24 hours following administration of digoxin 44 +/- 12% of the dose were recovered in urine of control subjects and 48 +/- 13% in patients with acute hepatitis, after methyldigoxin 34 +/- 5% and 34 +/- 8%, respectively. Metabolism of digoxin in patients with acute hepatitis was unaltered, whereas a diminished demethylation rate of methyldigoxin could be observed. 16 patients with acute hepatitis and 7 healthy volunteers received unlabelled digoxin p.o. as maintenance dose. Plasma glycoside concentrations were studied by radioimmunoassay. The average glycoside plasma concentrations were 0.59 +/- 0.21 ng/ml and 0.63 +/- 0.24 ng/ml, respectively.

Animals↗
PubMed1978

[Determination of digoxin in serum. Comparison of radioimmunoassay and a heterogeneous enzyme immunoassay (author's transl)].

This paper describes the evaluation of a heterogeneous enzymeimmunoassay (EIA, subtype ELISA) for the determination of digoxin in serum. Results are compared with those obtained from a radioimmunoassay (New England Nuclear, 125I-Digoxin). The limit of detection is 0.3 microgram/1 (0.4 nmol/1). The range of the test is from 0.3 unto 5.0 microgram/1 (0.4--6.4 nmol/1). Within-batch precision ranged from 7 to 11%, between-batch precision from 8--14%. Pure digoxin, added to solutions of albumin and pooled sera, gave recoveries between 87 and 106%. 116 sera from patients taking digoxin exclusively yielded no systematic difference compared to the results of a radioimmunoassay (RIA) (equation of the bivariate regression CELISA = 0.954 . CRIA + 0.14 (microgram/1) (0.18 nmol/1). Nevertheless marked differences between both tests were observed in individual cases. Digitoxin yielded in vitro and in vivo a cross-reactivity of 7 to 14% depending upon the concentration. In 68 sera from patients, taking digoxin plus spironolactone, we found results that were on average 0.48 microgram/1 (0.64 nmol/1) higher with the ELISA than with the RIA (p less than 0.01%). With respect to practicability the ELISA test for digoxin is very similar to the analogous RIA both using the solid phase technique.

Cross Reactions↗
PubMed1978

[Metabolism of meproscillarin in man (author's transl)].

The investigations on the metabolism of 14-Hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) were performed in 5 healthy test persons as well as in 4 patients with biliary fistula, applying a single oral dose of 0.5 mg of 3H-meproscillarin. The elimination half-life of total plasma radioactivity was about 51 h in the test persons, and 18 and 30 h in the patients whose bile was drawn off via a T-drain. The test persons excreted about 20% of total radioactivity renally and about 56% with the faeces. The patients excreted between 29% and 89% of the radioactive dose applied with the bile, the major part being eliminated already after 24 h. Up to 3% was excreted with the faeces. Renal excretion varied between 6% and 22%. Total radioactivity in plasma, bile, urine and faeces was separated into chloroform-soluble and chloroform-insoluble fractions, which were further differentiated by thin-layer chromatography. Whereas in plasma, bile and urine mainly chloroform-insoluble metabolites of meproscillarin were present, the chloroform-soluble fraction in the faeces represented the major portion, also containing primarily meproscillarin. The results are discussed.

Adult↗
PubMed1978

Human myocardium and plasma digoxin concentration in patients on long-term digoxin therapy.

Digoxin concentration of 14 left ventricular papillary muscles and 36 right atrial appendages of 45 patients undergoing cardiac surgery were determined by the NEN 125J-radioimmunoassay. Blood specimens for digoxin assay were withdrawn immediately before operation, 12 to 16 hr after the last digitalis dose. Mean papillary muscle digoxin concentration was 76.1 ng/g +/- 25.5; mean ratio to plasma digoxin level, 36.8:1. The mean concentration of right atrial appendages was 41.8 ng/g; mean ratio, 29.9:1. Most of the tissue specimens were examined histologically using Hematoxylin-Eosin and van Gieson stains. No clear relation between tissue digoxin concentration and hisological alteration, i.e., the degree of fibrosis or lipomatosis, could be found, although most severe alterations were found in right atrial appendages corresponding to a higher variation in tissue concentrations and a poorer correlation to plasma digoxin (r = 0.47, respectively for papillary muscle r = 0.73).

Adult↗
PubMed1977

Overall pharmacokinetics during prolonged treatment of healthy volunteers with digoxin and beta-methyldigoxin.

Five healthy volunteers received digoxin 0.4 mg or beta-methyldigoxin 0.4 mg i.v., daily for 14 days, in a randomized cross-over arrangement. By monitoring minimal plasma concentrations during multiple dosing, it was found that the steady state pharmacokinetics of digoxin and beta-methyldigoxin could be estimated even better by a one-compartment than by a two-compartment model. The following mean parameters were calculated: the half life of digoxin of 1.54 +/- 0.31 days was significantly shorter than the half life of 2.29 +/- 0.34 days for beta-methyldigoxin. The distribution volume of 807 +/- 187 liters for digoxin was not significantly larger than the 735 +/- 227 liters for beta-methyldigoxin. Renal digoxin clearance of 191 +/- 25 ml/min was significantly higher than both the renal clearance of beta-methyldigoxin of 111 +/- 23 ml/min and also the creatinine clearance, which indicates tubular secretion of digoxin. There was a 2.8-fold accumulation of beta-methyldigoxin injected once a day, which was significantly higher than the 1.80-fold accumulation of digoxin.

Adult↗
PubMed1977

[The biological availability of digitoxin].

The bioavailability of digitoxin after a single dose of 0.5 mg was studied in 6 healthy volunteers by estimation of tmax, cmax, AUC und urinary excretion rate. After tablets, absorption was rapid, after dragées delayed. The mean t1/2 of digitoxin for i.v. administration was 9.5 +/- 0.9 days, for oral administration of tablets 7.4 +/- 0.5 days and for dragées 9.7 +/- 2.0 days. The cumulative recovery of glycosides in urine during the first 48 hours was higher after tablets than after i.v. administration. The shorter t1/2 of digitoxin after tablets compared with the longer t1/2 after gastric juice resistent dragées demonstrated the presence of a substantial extrahepatic "first pass"-effect by degradation of digitoxin before absorption. Such mechanism would partly explain the shorter t1/2 after digitoxin-tablets due to an increased elimination of splitting products. By extrapolation to t-infinite AUC and urinary excretion rates were not significantly different between various formulations. The mean absolute bioavailability of digitoxin-dragées amounted to 82-88 percent and the relative bioavailability of digitoxin-tablets to 84-93 percent.

Administration, Oral↗
PubMed1977

[Biologic availability and "1st pass" effect of drugs].

Bioavailability and "first pass"-effect are of increasing importance in Clinical Pharmacology. Bioavailability is the rate and above all the extent to which a drug reaches the systemic circulation. Reduced bioavailability may result from the physico-chemical properties of the drug, its solubility in the intestinal tract and its ability to permeate the gut wall. Reduced bioavailability may also result from a "first pass"-effect if the drug is metabolized during absorption by the enteral mucosa or during its first liver passage. Some conclusions may be drawn which are of importance for the clinic and pharmacy from the presented empirical and theoretical examples.

Administration, Oral↗
PubMed1977

[Plasma-digoxin concentration in patients at time of hospital admission (author's transl)].

Plasma-digoxin and serum creatinine concentrations were determined on admission in 145 unselected patients previously digitalized as outpatients. Adequate digitalization was found in 62.7%, inadequate doses in 15.9% of patients. In the latter group the daily dosage reported by the patients failed to correlate with the plasma-digoxin concentration by radioimmunoassay. One-fifth of all patients had clinical evidence of digitalis intoxication. Of these, 69% had plasma-digoxin concentrations of more than 2.0 ng/ml and 31% less than 2.0 ng/ml. Mean digoxin concentration for all patients with signs of digitalis intoxication was 2.5+/-0.9 ng/ml. In patients simultaneously receiving spironolactone or canrenoate-K+ there was danger of falsely high values for digoxin because of interference of those drugs with the radioimmunoassay.

Ambulatory Care↗
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↗
PubMed1977

[Radioimmunological estimation of digoxin in urine (author's transl)].

When separating free and antibody bound digoxin, dextrancoated charcoal suspensions in protein-free urine dilutions develop an improve sieve effect which improves with aging of the suspensions. On addition of albumin to the dilution medium (buffer), the adsorptive capacities become stabilized. In urine dilutions less than of 1:50, false positive digoxin concentrations were measured. Determinations of 0-5 ng digoxin/ml in the diluted urine (1:100) and in the buffer solution show identical results. The recovery of added digoxin (1 ng and 2 ng/ml) is 100%; the lower detection limit is 3.6 mug/l urine. Between-assay variation for means of duplicates shows in the main measuring range (1.5-2.8 ng digoxin/ml) a variation coefficient less than of 4.5%; for a commercial test this value is distinctly higher. Dihydrodigoxin is measured at 3% only. Application of this method for measuring cumulative glycoside elimination of 5 healthy persons (0.5 mg digoxin daily intravenously during 2 weeks) results in a minimal interindividual variation of 5.1%. In a test preparation with a bioavailability of 94.6% the variation is 5.2%.

Biological Availability↗
PubMed1977

[Pharmacokinetics of cardiac glycosides and clinical consequences].

The purpose of pharmacokinetics of cardiac glycosides is to study the time courses of glycosides in biological fluids, tissues and excreta. The extent of accumulation of a given dose at uniform time intervals depends only from the overall elimination rate constant. By knowing the elimination rate constant the extent to which a cardiac glycoside would accumulate in the body following a fixed dosing regimen can be calculated. The higher accumulation in the central nervous system requires a much longer time. Therefore it may be assumed that the brain is a deep compartment for cardiac glycosides and this compartment cannot be detected by analysis of plasma glycoside concentrations. Central side effects of cardiac glycosides may occur at therapeutic plasma levels. In renal disease a lower maintenance dose of digoxin and methyldigoxin should be administered or the same dose less frequently. Digitoxin does not accumulate in patients with renal failure or in anuria since the extrarenal elimination of digitoxin is much higher compared to digoxin and methyldigoxin.

Biological Availability↗