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  • 1
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 885-886 
    ISSN: 1432-1440
    Keywords: Cephalosporins ; Vitamin K1-epoxide ; Coumarin-like action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In three patients treated with cephalosporins (one patient with latamoxef, two patients with cefazedone) vitamin K1 was injected to investigate whether this was followed by an increase in vitamin K1 2,3-epoxide plasma concentrations as compared to controls. Such a rise in K1-epoxide concentrations in the plasma can be demonstrated following treatment with coumarins. This reflects an inhibition of the vitamin K1-epoxide reductase in the liver. Coumarins are thought to induce hypoprothrombinaemia by such a mechanism. In all three patients we found a considerable increase in the vitamin K1-epoxide plasma concentrations following injection of 10 mg vitamin K1, whereas in normal subjects only traces of K1-epoxide could be detected (〈0.030 µg/ml). The K1-epoxide concentrations found in our three patients treated with cephalosporins were 0.12, 0.16 and 0.19 µg/ml, respectively. This indicates that latamoxef or cefazedone might reduce clotting factor synthesis by a coumarin-like mechanism of action in these patients. Although the effect of cephalosporins in enhancing vitamin K1-epoxide plasma concentrations is less than that of coumarins, it might cause severe hypoprothrombinaemia in the presence of latent vitamin K deficiency.
    Type of Medium: Electronic Resource
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