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  • RIA  (1)
  • diltiazem  (1)
  • Springer  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 197-202 
    ISSN: 1432-1041
    Keywords: digoxin ; hydrolysis metabolites ; enteric coating ; dihydrodigoxin ; liquid chromatography ; RIA ; urine ; plasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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〉0.05). The discrepancy was mainly due to significantly greater excretion of dihydrodigoxin after the capsule ( $$\bar m$$ 12.8%, range 0–28.6% of the dose) than after the digoxin solution ( $$\bar m$$ 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〈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. Thus, the enteric-coated digoxin preparation delayed the absorption and reduced the hydrolysis of the glycoside, but it also carried the drawback of reducing digoxin availability, mainly because of increased metabolism to dihydrodigoxin.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 427-433 
    ISSN: 1432-1041
    Keywords: Hypertension ; diltiazem ; metoprolol ; adverse effects ; multicentre study group
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double-blind, parallel-group multicentre study has been done to compare the antihypertensive properties, effects on serum lipoproteins and adverse effect profiles of diltiazem and metoprolol given as monotherapy to primary hypertensive patients. 128 patients were included from 10 participating centers. Following a placebo wash-out period of 5 weeks, patients were randomized either to diltiazem or metoprolol treatment according to a forced titration regimen. Each dose was given for a 4-week period in a stepwise regimen. A total of 119 patients, 59 and 60 in the two groups, completed the study. Supine and standing BPs were reduced in a similar, dose-dependent fashion by diltiazem and metoprolol. In the former supine BP fell from 161/101 to 151/91 mm Hg at the highest dose level. In the latter patients, supine BP at the highest dose level was reduced from 161/102 to 155/94 mm Hg. Target pressures (DBP ≤ 90 mm Hg and/or DBP reduction of ≥ 10%) were reached in 63% and 48% of the patients, respectively. HDL-cholesterol was increased in diltiazem-treated patients and decreased in those on metoprolol. Otherwise, serum lipoproteins did not differ significantly between treatments. The incidence and severity of dose-dependent adverse effects did not differ significantly between treatments, although moderate to distressing side effects were reported more commonly by metoprolol-treated patients. Ankle oedema and breathlessness tended to be more common on diltiazem therapy, while tiredness, increased sweating and sleep disturbances appeared to be experienced more frequently by metoprolol-treated patients. Thus, when given as monotherapy, the daily dose-ranges for a comperable reduction in BP were 120–360 mg diltiazem and 50–200 mg metoprolol. Within those dose-ranges, the antihypertensive efficacy and the overall incidence of adverse effects did not differ between the treatments. As monotherapies, diltiazem and metoprolol are both suitable for the management of mild to moderate hypertension.
    Type of Medium: Electronic Resource
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