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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 23 (1984), S. 5090-5095 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 695-702 
    ISSN: 1432-1041
    Keywords: pharmacokinetic theory ; gamma distribution ; residence time ; circulation time ; absorption time ; physiological model ; data evaluation ; concentration-time profil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using a nonclassical statistically based pharmacokinetic concept, a theory is presented which can be applied to the analysis of concentration-time data fitted by power functions of time C=At−ae−bt, which is shown to be equivalent to the assumption of gamma distributed residence times of drugs. The shape and scale parameters a and b, respectively, are interpreted physiologically in terms of a recirculatory model. It is shown how the shape parameter a, which is only dependent on the coefficient of variation of residence times, is affected by the processes of drug distribution and elimination. The time course of the blood concentration following multiple doses and continuous infusion is predicted for gamma-like drug disposition curves. The assumption of gamma distributed disposition residence times is theoretically based on a random walk model of circulatory drug transport, and the conditions are investigated under which gamma curves can be empirically fitted to oral concentration-time data. The parameters of concentration-time profiles following solid dosage forms, for example, are explained by the means and coefficients of variation of the disposition residence time and dissolution time distribution, respectively. The advantages of this concept compared to the conventional method of fitting sums of exponentials to the data are described.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 355-359 
    ISSN: 1432-1041
    Keywords: drug accumulation ; reliability theory ; multiple dosing ; curve moments ; mean disposition residence time ; cumulative urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bounds of the accumulation profile can be predicted on the basis of the mean disposition residence time (MDRT) of a drug. The time to reach 90% of the plateau level (t 0.9) is less than 3.7 MDRT. This prediction can be improved if, in addition, the variance of disposition residence time (VDRT, CV D 2 =VDRT/MDRT2), or the terminal exponential coefficient (λ), is known. For CV D 2 →1 or λ MDRT→1, the time to reach steady state (t0.9) approaches 2.3 MDRT (limiting case of monoexponential drug disposition curve). Conditions are stated under which λ can be regarded as the principal determinant of the accumulation rate.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 121-126 
    ISSN: 1432-1041
    Keywords: recirculation model ; initial distribution volume ; pharmacokinetic model ; residence time distribution ; cardiac output
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Based on a recirculatory pharmacokinetic model, a physiologically realistic definition of the initial distribution volume has been developed to characterize the overall distribution process occuring shortly after rapid bolus injection of a drug. This apparent volume of distribution, which refers to the peak right atrial blood concentration, depends on the cardiac output and basic pharmacokinetic parameters usually derived from the whole blood concentration vs time curve. The initial distribution process appears to be affected by changes in the variance of the distribution of residence times of the drug in the body. The influence of the site and time of early blood sampling on the estimated initial distribution volume is discussed. This relatively simplea priori model should prove useful in predicting to a first approximation the principal characteristics of the initial distribution process.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 455-457 
    ISSN: 1432-1041
    Keywords: digoxin ; concentration plateau ; pharmacokinetics ; systolic time intervals ; optimal infusion scheme ; dose-response data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using a volume-controlled infusion pump, a mean serum plateau level of digoxin of 4–5 ng/ml was rapidly achieved and maintained in 6 healthy volunteers. The infusion scheme was calculated on the basis of data published on the pharmacokinetics and pharmacodynamics of digoxin following bolus intravenous injection. The magnitude of the response (change in electromechanical systole) at the end of the plateau phase was comparable to that observed with the concentration in the therapeutic range at steady state.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of mathematical biology 15 (1982), S. 305-318 
    ISSN: 1432-1416
    Keywords: Pharmacokinetics ; Linear recirculatory model ; Tissue distribution process ; Transit time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract Characterizing the tissue distribution kinetics of drugs by physiological and physico-chemical parameters and using a circulatory model the time course of blood concentration after intravenous injection is predicted for linear pharmacokinetic systems. The interrelationships between the first three (zero to second) moments of the distribution functions of organ transfer times, circulation times and residence times of drug molecules in the body are described. Utilizing literature data the model is applied to the analysis of lidocain kinetics in humans.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of mathematical biology 20 (1984), S. 95-102 
    ISSN: 1432-1416
    Keywords: pharmacokinetics ; generalized inverse Gaussian distribution ; recirculatory model ; renewal theory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract Based on a stochastic pharmacokinetical model (which mirrors topological properties of the circulatory system) it is shown by reinterpreting results of Wise (1974) that if the transit times of circulating drug molecules have a generalized inverse Gaussian distribution the corresponding residence times are gamma distributed. The condition that the probability of elimination of a drug molecule in a single circulatory passage is sufficiently small appears to be valid for most drugs. Thus theoretical evidence is given for fitting blood concentration-time curves following bolus injection of a single dose by power functions of time.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 30 (1981), S. 193-195 
    ISSN: 1570-7458
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 318 (1984), S. 273-275 
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 319 (1984), S. 826-830 
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Zusammenfassung Die Festigkeit von Hartmetallen auf Basis WC-Co hängt u. a. auch von der Kohäsionsenergie der Carbid-Carbid-Korngrenze im Gefüge ab. Geringe Mengen von Spurenelementen, die sich an diesen Stellen anreichern, können die Bruchfestigkeit der Hartmetalle beeinträchtigen. Anhand von Scanning-Auger-Untersuchungen von frischen Hartmetallbruchflächen konnten wir nachweisen, daß zwischen den Carbidkörnern ein monoatomarer Cobaltfilm vorliegt. In titanhaltigen WC-Mischcarbidsystemen wird das Titan auch an den WC-WC-Korngrenzen angereichert. Die Chromverteilung an den Korngrenzen ist heterogen. Kritisch ist jedoch die Phosphorsegregation, die trotz geringer Gesamtkonzentrationen (2 ppm) zu beobachten war. Phosphor wird in den Hartmetallen einen ähnlichen Versprödungseffekt hervorrufen wie bei vielen technischen Stählen und Legierungen. Für die Untersuchung von Carbid-Carbid-Korngrenzen ist es zweckmäßig, den Co-Binder durch HCl-Behandlung herauszulösen. Dadurch wird der Anteil von Carbidkorngrenzen in der Bruchfläche wesentlich erhöht.
    Notes: Summary The mechanical strength of cemented carbide materials depends among other factors on the cohesion energy of the carbide-carbide grain boundaries. Small amounts of trace elements can segregate, reducing the mechanical properties of these materials significantly. We investigated fresh fracture surfaces of cemented carbide samples in a scanning Auger electron spectrometer and determined the chemical composition of the carbide grain boundaries. Based on these data it is confirmed that the binder metal cobalt forms a monolayer at the carbide-carbide grain boundaries. In titanium containing carbides titanium, too, segregates to the grain boundaries. Chromium was also observed, however, with a heterogeneous distribution. In spite of the low phosphorus content of 2 ppm it could be identified at the grain boundaries. It is to be expected that P develops an embrittling effect similar to that in technical steels. For the investigation of carbide-carbide grain boundaries it is advantageous to remove the Co binder by a HCl treatment. The remaining carbide skeleton fractures completely along the grain boundaries.
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