Effect of adjuvant therapy in primary breast cancer in relation to the estrogen receptor level.
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Biomedical subjects
Publications and source records attributed to S Gustafsson.
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A capsule preparation containing small, enteric-coated granules of digoxin was developed to prevent acid hydrolysis of the drug in the stomach and to diminish the variation in plasma glycoside concentration during the intervals between doses. The absorption and metabolism of tritiated digoxin after a single oral loading dose of this formulation (Formulation C) were compared to those after ingestion of a digoxin solution (Formulation S) by 8 healthy men. Drug concentrations were measured by radioimmunoassay (RIA) and liquid chromatography (LC). The percentage of the digoxin dose excreted in the urine during 72 h, as measured by RIA, was significantly lower after the capsule (20.5 +/- 2.0% vs 36.2 +/- 3.0% after S, mean +/- SEM) but total urinary radioactivity after the two treatments was similar (C 35.3 +/- 5.2 and S 41.2 +/- 2.6%; p greater than 0.05). The discrepancy was mainly due to significantly greater excretion of dihydrodigoxin after the capsule (m 12.8%, range 0-28.6% of the dose) than after the digoxin solution (m 5.4%, range 0-14.5%). Dihydrodigoxin was not measured by the RIA. The recovery of hydrolysis metabolites (LC) was greater during the first 24 h after S (2.3 +/- 0.6% vs 0.9 +/- 0.3% after C; p less than 0.05). The peak plasma concentration of digoxin (RIA) was significantly reduced and delayed after intake of C (2.5 +/- 0.4 nmol/l at 3.8 +/- 0.3 h vs. 8.3 +/- 0.8 nmol/l at 0.9 +/- 0.1 h after S), and so was the shortening of electromechanical systole at 1.5 h, 2.5 h, and 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Liquid chromatography with amperometric detection was employed for the determination of the dihydroxycatecholamine metabolites, 3,4-dihydroxyphenylethylene glycol (DOPEG) and 3,4-dihydroxyphenylacetic acid (DOPAC) in plasma. The compounds were isolated from plasma by adsorption onto alumina, the elution from which was found to be strongly dependent on the acid used. Conditions for the separation on octadecyl-bonded silica were evaluated with particular reference to the influence of pH, ion-pairing anions and quaternary ammonium ions. Recoveries of ca 85% and relative standard deviations of about 3% were obtained for the assay of endogenous concentrations.
The hydrolytic cleavage of digoxin was studied after single oral doses of tritiated glycoside to four patients with gastric hyperacidity (GH-group) and to six patients during coronary care (CCU-group). Drug analysis was performed with a high-pressure liquid chromatographic method. Results in the two groups did not differ and were similar to results in a previous study in healthy volunteers. On the average 22% of the radioactivity was recovered in 24-h urine specimen. Of this 24.8 +/- 8.5% (GH-group, mean +/- SEM) and 19.3 +/- 6.6% (CCU-group) were cleavage products and unidentified, polar metabolites in equal amounts. This indicates that hydrolysis of digoxin is on average limited even in patients at risk for such metabolic cleavage.
A liquid chromatographic method for the determination of free urinary concentrations of epinephrine, norepinephrine and dopamine is presented. For urine samples, pre-purified by adsorption onto alumina, ion-exchange chromatography was, in terms of selectivity, found to be superior to the more widely used reversed-phase chromatography. The column eluates were monitored with an electrochemical detector utilizing a glassy carbon working electrode. The method allows determination of the concentrations in 0.5 ml of normal urine samples with a relative standard deviation below 2%.
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