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  • 1
    Electronic Resource
    Electronic Resource
    Prolongation of the PQ interval as a measure of therapeutic inequivalence between two formulations of diltiazem (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 45-49 
    Details
    ISSN: 1432-1041
    Keywords: Diltiazem ; PQ interval ; ECG ; bioequivalence ; therapeutic equivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We studied the use of atrioventricular (AV) conduction time to assess the therapeutic equivalence of two diltiazem formulations in 20 volunteers in a double-blind, cross-over trial. ECG recording was carried out before and at several intervals after drug administration, and prolongation of the PQ interval (ΔPQ) was taken as a pharmacodynamic response. In addition, diltiazem plasma concentrations were determined in 8 subjects. The effect of diltiazem increased proportionally with the plasma concentration and could be detected up to 10 h after administration. The area under the effect-time curve (AUEC0–10), the peak effect (Emax), and the effect mean residence time (MRTE) showed significant differences. In contrast to the pharmacodynamics, the pharmacokinetic profiles of diltiazem do not vary to the same extent. We conclude that the formulations are therapeutically different. Furthermore, at the administered dose, ΔPQ appears to be a sensitive measure for assessing the electrophysiological properties of diltiazem.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00202171
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 1164-1168 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01733250
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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