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  • 1
    ISSN: 1573-7241
    Keywords: antiarrhythmic drugs ; flecainide ; concentrationdose relationship ; heart failure ; amiodarone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The trough concentration-dose (C/D) ratio of flecainide was prospectively studied in 78 patients with various cardiac arrhythmias. After the removal of two outlier values, no influence of body weight on C/D ratio was evidenced. Coadministration of amiodarone, and, moreover, the presence of heart failure increase the C/D ratio, from 2.01±0.78 to 2.55±0.37 and 2.9±1.19 ng/ml/mg, respectively (p〈0.001 by two-factor analysis of variance). The presence of both heart failure and amiodarone therapy increases the C/D ratio to 3.88±1.07 ng/ml/mg. A single loading oral dose (30 mg/kg) of amiodarone increased C/D measured at the sixth hour in nine patients from 2.27±0.50 to 2.57±0.73 ng/ml/mg (p〈0.05). The trough C/D ratio increased more during chronic treatment from 2.03±0.86 to 2.92±1.32 ng/ml/mg (p〈0.05). Thus, a dosage reduction of flecainide (of 50% in some cases) is mandatory, in case of heart failure or the combination with amiodarone therapy, to obtain a plasma level of the drug that is similar to those observed in patients with a normal heart and without amiodarone therapy. The flecainideamiodarone interaction seems time dependent.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 16 (1988), S. 311-327 
    ISSN: 1573-8744
    Keywords: population pharmacokinetics ; random regression ; distribution estimation ; nonparametric estimation ; maximum likelihood ; cyclosporine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new method, nonparametric maximum likelihood (NPML), for statistical analysis of population kinetic data is proposed. NPML provides a discrete estimate of the whole probability density function of the pharmacokinetic parameters. This permits a straightforward derivation of usual population characteristics. To illustrate the application of the NPML method, a population analysis of cyclosporine RIA measured plasma levels in 188 bone marrow transplant patients after intravenous infusion, is presented. The capability of NPML to extract population information from sparse individual data is also outlined.
    Type of Medium: Electronic Resource
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