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  • Articles  (6)
  • 1980-1984  (6)
  • Medicine  (6)
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  • Articles  (6)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 22 (1982), S. 117-122 
    ISSN: 1432-1041
    Keywords: digoxin ; quinidine ; sparteine ; inotropic effect ; plasma levels ; systolic time intervals ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of single doses of quinidine sulphate (Q) 0.5 g, sparteine sulphate (SP) 0.2 g, and placebo (PL) on heart rate-corrected systolic time intervals (STI) (QS2c, PEPc, LVETc) and on QTc duration was studied 2 and 4 h after treatment of six healthy volunteers. All measurements were done twice in a double blind fashion, once under digoxin (D) steady state (β-methyl digoxin 0.3 mg daily) and once after an equally prolonged basic treatment period with PL. All basic treatment periods and single dose periods were randomized. Drug effects were estimated by comparison with the results obtained after administration of the corresponding placebo. The data were analyzed by two-factorial multivariate analysis of variance. Steady state digoxin serum concentrations averaged 1.3 µg/l and there was no significant change following antiarrhythmic drugs compared to PL. Single oral doses of Q and SP resulted in mean serum concentrations of about 1.8 mg/l and 0.25 mg/l, respectively. In non-digitalized subjects Q 0.5 g resulted in a lengthening of QS2c (+15 ms), LVETc (+13 ms) and QTc (+65 ms). With SP 0.2 g similar but smaller effects were seen. D alone resulted in shortening of QS2c (−21 ms), LVETc (−14 ms), and QTc (−32 ms). Pretreatment with D did not influence the effects of Q on the various parameters. However, corresponding to the D-induced changes in STI, a parallel shift of the curve was observed. The effects of sparteine were somewhat reduced by D. Most of the effects of Q compared to PL and SP were statistically significant (p〈0.05) during both basic treatments, and the D basic treatment had a statistically significant effect for all treatment regimens, but there was no significant interaction between them. In contrast to others, the present results indicate that the positive inotropic effect of D persists in the presence of Q and SP, and that the antiarrhythmic drugs induce negative inotropic effects independent of basic treatment with D. Under the conditions of this experiment, each drug maintains its negative or positive effect on inotropy, thus resulting in an almost arithmetical superposition of the separate drug effects.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 287-292 
    ISSN: 1432-1041
    Keywords: ouabain ; nitroglycerin ; cardiac glycosides ; impedance cardiography ; systolic time intervals ; echocardiography ; cardiac load changes ; pharmacodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this intraindividual, placebo-controlled, double blind study the dynamic effects of single doses of ouabain 0.5 mg i.v. and 12 mg sublingual were compared with those of the vasodilator sublingual nitroglycerin 0.8 mg. In 12 (sublingual) and 6 (i.v.) healthy volunteers, respectively, cardiac performance was assessed for 60 min after administration, using systolic time intervals (QS2c, PEPc, PEP/LVET), electrical impedance cardiography ((dZ/dt)/RZ index) and echocardiography (EDD, ESD, FS). After i.v. ouabain the typical positive inotropic glycoside effects appeared (shortening of QS2c, PEPc, and PEP/LVET, increase of (dZ/dt)/RZ and FS, decrease of EDD and ESD). With nitroglycerin preload reduction diminished cardiac performance, as shown by a rise in PEPc and PEP/LVET and depression of (dZ/dt)/RZ. In addition, EDD (not significant) and ESD were somewhat reduced, FS was enhanced, and QS2c tended to shorten. Following sublingual ouabain, QS2c was unchanged, there was an increase in PEPc and PEP/LVET, a decrease in (dZ/dt)/RZ and FS, EDD was unchanged, and ESD rose. By this route the absolute magnitude of the effects was about 1/3 that of the i.v. drug action. The spectrum of effects of sublingual ouabain indicates a reduction in cardiac performance without any detectable inotropic action. The effects seem to be induced by load changes, with an indication of an increase in afterload although an additional preload reduction cannot be excluded. This dose of the drug given by the sublingual route appears, therefore, to alter cardiac function via an effect on the peripheral circulation, although the final mechanism has not yet been elucidated. It is not known whether these biological effects in healthy subjects may have any clinical significance in patients with cardiac disorders.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 22 (1982), S. 265-272 
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; variation of absorption ratios ; bioavailability ; dissection of variation due to absorption and intermediate processes ; oral drug application
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Differences in the plasma concentrations of drugs after oral administration are caused by two main factors: variation in absorption ratios and in the distribution processes in the body. A new method for the dissection of both types of factors is discussed. The method uses a reference regression of the AUC-values to the corresponding values after intravenous infusion of graded doses. The reference regression is estimated from an appropriate trial. Deviation of the determined AUC-values from the regression curve afford an estimate of the residual variance due to varying distribution volumes or similar random biological effects. For the estimation of absorption ratios after oral administration the drug is given orally to another sample of subjects and their AUC-values are calculated. The deviation of these AUC values due to the above mentioned random effects are simulated using the residual variance of the reference regression, and are subtracted from the observed AUC-values. Then, the differences in the corresponding absorbed doses are transformed by inverting the reference regression. From these doses the empirical distribution function and statistical parameters (e.g. quantiles) are determined. The method has the advantage that no restrictive assumptions are required, such as first order processes, dose linearity, homogeneity of variance or normal distribution of absorption ratios. Its applicability to substances with qualitative differences in their pharmacokinetics is demonstrated by appropriate examples.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 1982-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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  • 5
    Publication Date: 1982-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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  • 6
    Publication Date: 1984-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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