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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 313-316 
    ISSN: 1432-1041
    Keywords: diprafenone ; pharmacokinetics ; bioavailability ; first-pass metabolism ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the antiarrhythmic drug diprafenone have been investigated in 6 healthy volunteers following single intravenous (50 mg) and oral doses (50 and 150 mg). Diprafenone was mainly eliminated by metabolism in the liver. Following i.v. infusion of 50 mg diprafenone, the terminal half-life of elimination was 1.50 h, the volume of distribution at steady-state was 1.23 l·kg−1, and the free fraction in plasma was 1.68%. Mean total plasma clearance was 741 ml·min−1·70 kg−1, which approaches normal liver blood flow after correction for the blood/plasma concentration ratio. Thus, diprafenone can be classified as a high extraction drug. Following oral administration, a dose-dependent increase in bioavailability from 10.9 (50 mg dose) to 32.5% (150 mg dose) was observed. The data suggest that diprafenone is subject to saturable hepatic first-pass metabolism.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 579-582 
    ISSN: 1432-1041
    Keywords: diprafenone ; propranolol ; beta-adrenoceptor blocking activity ; antiarrhythmic drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The beta-adrenoceptor blocking activity of the new Class Ic-antiarrhythmic drug diprafenone has been determined in man in comparison with that of propranolol, using the standardized isoproterenol test. Following placebo, the dose of isoproterenol which increased the heart rate by 25 beats·min−1 (CD25) was 0.84 (0.1–2.72) µg (median and range). Two hours following single oral doses of 200 mg diprafenone (3.61 µg; 1.53–44.15) or 40 mg propranolol (16.06 µg; 9.15–27.04) significantly higher CD25-values were found. The affinity constants for the beta-adrenergic receptors calculated on the basis of free drug in the plasma were similar for propranolol and diprafenone (2.79 vs. 2.60 nM−1, respectively). Thus, diprafenone showed a definite degree of beta-blocking activity in a clinically relevant range of plasma concentrations.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Polymorphic drug oxidation ; Metoprolol ; Propafenone ; Diltiazem ; Sparteine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with IIIo AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (〉 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.
    Type of Medium: Electronic Resource
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