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  • population pharmacokinetics  (2)
  • S-PLUS library  (1)
  • concentrationdose relationship  (1)
  • 1
    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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  • 2
    ISSN: 1573-8744
    Keywords: mizolastine ; noncompartmental approach ; pharmacokinetic model ; bioavailability estimation ; nonlinear regression ; heteroscedastic variance ; S-PLUS library
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This paper presents the analysis of the kinetics of a new antihistamine, mizolastine, in 18 healthy volunteers, from concentrations measured after an intravenous infusion and two different oral administrations: tablet and capsule. Two approaches were used to analyze these data: (i) a noncompartmental approach implemented in PHARM-NCA: (ii) a compartmental modeling approach implemented in a new S-PLUS library. NLS2, 5 which allows the estimation of variance parameters simultaneously with the kinetic parameters. For the compartmental modeling approach, two-compartment open models were used. According to the Akaike criterion, the best model describing the kinetics of mizolastine after oral administration was the zero-order absorption model. The kinetic parameters obtained with PHARM-NCA and NLS2 were similar. The estimated duration of absorption was greater for the tablets than for the capsules (with means equal to 1.13 hr and 0.84 hr respectively). After an intravenous infusion, the mean estimated clearance was 4.9 L/hr, the mean λ 2 -phase apparent volume of distribution was 89.6 L and the mean terminal half-life was 12.9 hr.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 26 (1998), S. 689-716 
    ISSN: 1573-8744
    Keywords: experimental design ; population pharmacokinetics ; D-optimality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The expectation of the determinant of the inverse of the population Fisher information matrix is proposed as a criterion to evaluate and optimize designs for the estimation of population pharmacokinetic (PK) parameters. Given a PK model, a measurement error model, a parametric distribution of the parameters and a prior distribution representing the belief about the hyperparameters to be estimated, the EID criterion is minimized in order to find the optimal population design. In this approach, a group is defined as a number of subjects to whom the same sampling schedule (i.e., the number of samples and their timing) is applied. The constraints, which are defined a priori, are the number of groups, the size of each group and the number of samples per subject in each group. The goal of the optimization is to determine the optimal sampling times in each group. This criterion is applied to a one-compartment open model with first-order absorption. The error model is either homoscedastic or heteroscedastic with constant coefficient of variation. Individual parameters are assumed to arise from a lognormal distribution with mean vector M and covariance matrix C. Uncertainties about the M and C are accounted for by a prior distribution which is normal for M and Wishart for C. Sampling times are optimized by using a stochastic gradient algorithm. Influence of the number of different sampling schemes, the number of subjects per sampling schedule, the number of samples per subject in each sampling scheme, the uncertainties on M and C and the assumption about the error model and the dose have been investigated.
    Type of Medium: Electronic Resource
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  • 4
    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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