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Biomedical subjects

B Bergdahl

Publications and source records attributed to B Bergdahl.

36 records · Page 2Linked to original sources
PubMed1983

Fasting and postprandial absorption of digoxin from a microencapsulated formulation.

The absorption of digoxin from a capsule preparation containing a large number of small, enteric-coated granules of the glycoside (Preparation CR) was compared in 10 volunteers with that from a rapidly dissolving tablet (Preparation L). Plasma and urine digoxin concentrations were measured by radioimmunoassay. In the fasting state, after a loading dose of digoxin (0.76 mg), peak plasma concentrations were significantly (p less than 0.001) lower after CR (2.0 +/- 0.5 nmol/l, mean +/- SD) than L (4.7 +/- 1.1 nmol/l). Peak concentrations after CR were significantly (p less than 0.001) delayed compared to L (3.3 +/- 0.6 h vs 1.1 +/- 0.4 h). Also, postprandial peak plasma concentrations at steady state, were significantly (p less than 0.01) lower after CR (1.0 +/- 0.3 nmol/l) than L (2.7 +/- 0.5 nmol/l), and the peak concentrations occurred later (3.9 +/- 1.7 h vs 1.4 +/- 0.9 h). The area under the plasma concentration-time curves was smaller (p less than 0.01) for CR (17.7 +/- 5.9 nmol X 1(-1) X h) than for L (22.4 +/- 4.1 nmol X 1(-1) X h), and so was the amount of drug excreted in urine (174 +/- 25 micrograms vs 190 +/- 31 micrograms; p less than 0.005). Thus, the absorption rate of digoxin from the enteric-coated formulation was markedly reduced but at the cost of a variable reduction in the amount absorbed.

Adult↗
PubMed1983

Reproducibility of standard preparation in digoxin radioimmunoassay in plasma and serum.

We studied the reproducibility of standard preparations in digoxin radioimmunoassay in a randomized trial using serum and plasma as matrices. The errors expressed relative to the observed counts per minute (cpm) attributable to each of the procedures involved in the preparation of standards were as follows: preparation of stock solutions and dilutions, 1.3%; addition of diluted solutions to the medium, 1.2%; and residual error due to the assay procedure, 3.7%. No error caused by mixing, portioning, and storage was detected. Heparinized plasma gave lower cpm values than serum at 4.0 ng/ml (p less than 0.01), an effect that would give over- or underestimations by about 5% at that level, depending on the medium used. This suggests that standard and sample matrices should be similar. Our procedure for preparing the standards seems to be reasonably reliable; this is necessary for satisfactory monitoring of patients on digitalis therapy.

Digoxin↗
PubMed1982

Metabolism of digoxin and absorption site.

After oral intake of enteric-coated granules containing [3H]-digoxin extensive metabolism was observed. Maximum 66% of the 24 h urinary excretion was identified as [3H]-dihydrodigoxin, using high performance liquid chromatography for the analysis. It is suggested that metabolism of digoxin may depend on the absorption site.

Biotransformation↗
PubMed1980

Absorption of digoxin from a new microencapsulated formulation.

The absorption of digoxin from two capsule preparations containing a large number of small, enteric-coated granules of the glycoside (0.38 mg) was compared with that of the same amount from ultrarapidly dissolving commercial tablets. Eight volunteers were studied during steady state conditions. Digoxin concentrations in plasma and urine were measured by radioimmunoassay. Peak plasma concentrations of digoxin were significantly (p < 0.01) delayed after taking the capsules (2.6 +/- 1 h and 2.6 +/- 0.9 h, mean +/- SD) as compared to the tablets (1.3 +/- 0.7 h). The peak concentrations produced by the capsules were 3.1 +/- 1.0 and 2.6 +/- 1.1 nmol/l; only the latter was significantly (p less than 0.05) lower than after the tablets (3.4 +/- 1.0 nmol/l). Areas under the plasma concentration-time curves during a 24 h dosage interval were similar for the three preparations, and so was the 24 h urinary excretion of digoxin, which averaged 60-63% of the daily dose. Thus, this particular enteric coating of digoxin delayed absorption without reducing the amount absorbed.

Adult↗
PubMed1980

An evaluation method providing confidence intervals applied to radioimmunoassay.

A method for evaluation of radioimmunoassay results is described. The order of the single tubes in each assay run is randomized. A polynomial is fitted to untransformed data (y = counts per minute; x = concentration of curve.A confidence interval is calculated for each sample, taking into account the variance of the standard curve and that of the actual duplicate assay jointly.

Humans↗
PubMed1979

Inter and intra laboratory variation of digoxin radioimmunoassay in Sweden.

Samples from two pools were sent 10 times to 27 laboratories for assay of digoxin. One pool contained digoxin 2.60 nmol/l in normal plasma (SP); the other was pooled plasma from patients treated with digoxin (PP). Ten radioimmunoassay (RIA) methods were used. The mean of SP assays was 2.59 nmol/l, not significantly different from 2.60 nmol/l. The mean of PP determinations was 2.46 nmol/l. Within each of the 10 assay rounds, the concentrations showed an almost twofold variation and S.D. averaged 0.33 nmol/l and 0.31 nmol/l for SP and PP respectively. Significant differences (P less than 0.001) were found between mean concentrations obtained for the pools at various laboratories (SP range 2.15-2.85 nmol/l; PP range 2.12-2.72 nmol/l). The laboratory means obtained for SP and PP correlated significantly (P less than 0.001). Nevertheless, significant (P less than 0.01) variations between laboratories were found also concerning the mean difference between SP and PP concentrations. The interassay SD of the assays differed significantly between laboratories (range 0.05-0.61 nmol/l. Between and within groups of laboratories using the same RIA method and between various types of laboratories, differences were also found concerning both accuracy and precision of the assays. It is concluded that a better control of digoxin assay is needed.

Digoxin↗
PubMed1979

Disposition rate of proscillaridin A in man after multiple oral doses.

After multiple oral doses, the disposition rate constant (beta) of proscillaridin was studied in 4 young healthy volunteers and 33 elderly patients with congestive heart failure. Glycoside activity in plasma was assayed by the 86Rb-technique. In the volunteers the beta averaged 0.0299 corresponding to a half-life (t 1/2) of 23 h. beta could be determined in 24 patients and was 0.0139 +/- 0.0077 (mean +/- SD). The SD of beta due to biological factors was estimated to be 0.0072. The total variation of beta was 10fold. The mean beta corresponded to a t 1/2 of 49 h with a range from 19 to 209 h. It is concluded that the great variation of beta means difficulty in obtaining adequate plasma levels of proscillaridin and that a rapid elimination of the glycoside cannot be presumed.

Administration, Oral↗
PubMed1979

Four kits for plasma digoxin radioimmunoassay compared.

We evaluated four commercial radioimmunoassay kits for digoxin. We assayed a standard plasma containing digoxin, 2.0 microgram/L, and samples from patients receiving digoxin, with use of the kits and of a bioassay, the 86Rb-uptake inhibition technique. Intra-assay precisions differed significantly. Computer-calculated 95% confidence intervals for the radioimmunoassays averaged 0.4 to 0.6 microgram/L at the proposed toxic threshold of 2.0 microgram/L; the corresponding value of the 86Rb assay was 0.75 microgram/L. Digoxin in the standard plasma was overestimated with three of the kits (means: 2.40, 2.56, and 2.59 microgram/L) but was assayed accurately by the 86Rb technique and by one kit. This same kit gave a significantly lower mean (1.07 microgram/L) for the patients' samples then did the other three kits (1.32, 1.49, and 1.29 microgram/L), two of which also differed significantly in accuracy. The 86Rb assay measured glycoside activity corresponding to a mean digoxin concentration of 1.35 microgram/L. We conclude that the relatively low precision of digoxin assay and the variations in accuracy between kits from various vendors apparently deserve continual attention.

Digoxin↗
PubMed1978

Lidocaine and the quarternary ammonium compound QX-572 in acute myocardial infarction. A comparative study.

Patients with suspected or proven acute myocardial infarction complicated by ventricular arrhythmias not corrected by lidocaine therapy (bolus dose 100 mg followed by infusion 2 mg/min) were treated either with an increased dose of lidocaine (bolus dose 50 mg followed by infusion 3 mg/min) or with 600 mg N,N-bis dimethylammonium chloride (QX-572, Astra, Sweden) as an i.v. infusion during 30 min (3 patients) or 60 min (13 patients). In the lidocaine group the arrhythmias were controlled in 6 out of 15 patients, in the QZ-572 group in 12 out of 16, a difference that is not statistically significant. However, the frequency of side-effects was significantly higher (p less than 0.001) in the QX-572 group (15 out of 16 patients). They were also more severe, including pronounced tachycardia and hypertension. It is concluded that despite the high antiarrhythmic effect of QX-572, an increase of the lidocaine dose would be safer and preferable in the clinical situation studied.

Acute Disease↗
PubMed1977

Stability in vitro of methylproscillaridin.

The in vitro stability of methylproscillaridin has been compared with that of proscillaridin, the activities of the glycosides being assayed by the 86Rb-technique. After incubation in gastric juice at pH 1,2, and 3, the activity half life of each glycoside was proportional to pH and was approximately 0.25 h, 2.5 h, and 25 h, respectively. The inactivation rate in pure hydrochloric acid at pH 2 did not differ from that in gastric juice of the same pH. The glycosides were stable in bile and enteric juice. In faeces, methylproscillaridin was stable and proscillaridin was inactivated with a half life of 32 h. It is concluded that the difference in biological availability between the two glycosides cannot be explained by differences in gastrointestinal stability.

Bile↗
PubMed1977

Biliary excretion and enterochepatic recycling of proscillaridin A after oral adminstration to man.

A single oral dose of proscillaridin A (1.0-1.5 mg) was given to six patients with T-tube drainage of the common bile duct, and simultaneous samples of bile and plasma were collected at various times during the following 24 hours. Glycoside activity was assayed by the 86Rb-uptake inhibition technique. Peak activities in plasma (mean 0.80 ng/ml) were attained after 0.5-2h, and in bile (mean 6.9 ng/ml) after 1-4h. Subsequently, proscillaridin activity in bile was less than 5 ng/ml for the remainder of the sampling period, and 10-100 times higher than that in plasma. Bile samples treated with beta-glucuronidase and sulphatase showed 100-200 fold increase in glycoside activity. Deconjugation was also produced by treatment with enteric contents. The results suggest that conjugation of unchanged proscillaridin is a major metabolic route. After excretion in the bile, the conjugates may be split in the intestine and reabsorbed as active glycoside.

Administration, Oral↗
PubMed1977

Proscillaridin activity in portal and peripheral venous blood after oral administration to man.

The absorption of proscillaridin A was studied in four patients undergoing catheterization of the portal vein for diagnostic purposes. Proscillaridin 1.5 mg was given as a single oral dose and plasma glycoside activity was analyzed by the 86Rb-uptake inhibition technique. Proscillaridin appeared rapidly in the portal blood, peak activity being found after 15 min in three and after 30 min in one patient. In peripheral blood the peak activity occurred after approximately 35 min. Despite rapid passage across the gut wall, porto-peripheral differences in glycoside activity were small; they were zero after 4h. The mean amount absorbed as active porscillaridin during the first 4h after the dose was calculated to be only 7.1% of the given amount. Late porto-peripheral differences, probably due to enterohepatic recycling, appeared after 6h in three patients; The results suggest that proscillaridin undergoes first pass inactivation in the gut wall. Enterohepatic recirculation may contribute to the amounts of active glycoside that reach the systemic circulation.

Administration, Oral↗
PubMed1977

Activities of proscillaridin A in thoracic duct lymph after single oral doses in man.

In order to study the possibility that orally administered proscillaridin after absorption is transported by the lymph to the systemic circulation, the concentrations of the glycoside in thoracic duct lymph were analyzed in two patients with thoracic duct drainage. They received the drug as a single oral dose; plasma and lymph concentrations were measured by 86Rb-technique. Lymph was collected at various intervals for 24 hrs. The proscillaridin activity in thoracic duct lymph was low and followed closely that the plasma. During the sampling period, a total of 300 ng and 240 ng, respectively, was recovered in the lymph, corresponding to less than 0.03% of the administered dose. The results indicate that proscillaridin is not transported by the thoracic duct lymph.

Administration, Oral↗
PubMedDate not supplied

Excretion of digoxin and its metabolites in urine after a single oral dose in healthy subjects.

The 3-day urinary excretion of digoxin, its conjugated and unconjugated hydrolytic metabolites and dihydrodigoxin, was studied in 8 healthy men after oral administration of tritiated digoxin. Analysis was performed by high pressure liquid chromatography (HPLC). The total radioactivity corresponded to 45.4 +/- 2.0 per cent (mean +/- S.E.M.) of the dose. By HPLC 42.4 +/- 2.7 per cent was recovered before and 44.0 +/- 2.7 per cent after deconjugation of the samples. Digoxin and dihydrodigoxin constituted 40.3 +/- 2.9 per cent; of this 0.7 +/- 0.4 per cent was dihydrodigoxin. The sum of the hydrolytic metabolites was 2.1 +/- 0.3 per cent before and 3.4 +/- 0.5 per cent after deconjugation. No correlation was found between gastric pH and the production of hydrolytic metabolites. The relative amount of these metabolites was maximal (mean 13.4 per cent of the excretion) in the 4-8 h sampling period. During the first 8 h an average of 8.6 per cent of the radioactivity was not recovered by HPLC. The metabolism of digoxin as judged by urinary excretion was limited and showed great variation during the early hours after treatment. The excretion of unchanged digoxin in some individuals constituted as little as 60 per cent over the first 12 h after dosing.

Adult↗
PubMedDate not supplied

Increased psychosocial strain in Lithuanian versus Swedish men: the LiVicordia study.

OBJECTIVE: Coronary heart disease (CHD) mortality is four times higher in 50-year-old Lithuanian men than in 50-year-old Swedish men. The difference cannot be explained by standard risk factors. The objective of this study was to examine differences in psychosocial risk factors for CHD in the two countries. METHODS: The LiVicordia study is a cross-sectional survey comparing 150 randomly selected 50-year-old men in each of the two cities: Vilnius, Lithuania, and Linköping, Sweden. As part of the study, a broad range of psychosocial characteristics, known to predict CHD, were investigated. RESULTS: In the men from Vilnius compared with those from Linköping, we found a cluster of psychosocial risk factors for CHD; higher job strain (p <.01), lower social support at work, lower emotional support, and lower social integration (p values <.001). Vilnius men also showed lower coping, self-esteem, and sense of coherence (p values < .001), higher vital exhaustion, and depression (p values < .001). Quality of life and perceived health were lower and expectations of ill health within 5 to 10 years were higher in Vilnius men (p values < .001). Correlations between measurements on traditional and psychosocial risk factors were few and weak. CONCLUSIONS: The Vilnius men, representing the population with a four-fold higher CHD mortality, had unfavorable characteristics on a cluster of psychosocial risk factors for CHD in comparison with the Linköping men. We suggest that this finding may provide a basis for possible new explanations of the differences in CHD mortality between Lithuania and Sweden.

Coronary Disease↗