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  • 1
    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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  • 2
    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.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    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.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 48 (1982), S. 163-170 
    ISSN: 1432-1106
    Keywords: Raphe ; Cerebellum ; Harmaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The firing patterns of single raphe units at the posterior midbrain level were examined in chloralosed rats to assess the effects of cerebellar stimulation and/or harmaline administration. Raphe cells were grouped according to their spontaneous firing rate and other characteristics into two categories. From a total sample of 160 cells, 106 (66%) presenting a slow regular discharge pattern were classified as serotonergic (5-HT cells), whereas 35 (22%), having a faster firing rate, were considered non serotonergic (NS cells). Moreover, 19 (12%) raphe units were non categorized. Cerebellar juxtafastigial (JF) stimulation modified the discharge pattern of 56 (35%) raphe units. The remaining 65% were unaffected by the stimulation. Of the 41 5-HT cells affected by JF stimulation, 28 neurons (68%) showed a systematic increase of their firing rate, whereas of the 12 NS cells affected 8 neurons (66%) were inhibited. It thus appears that cerebellar stimulation has an opposite effect on raphe units according to the cell types. Harmaline administration suppressed the activity of 5-HT cells and increased the discharge rate of NS cells. Moreover, we noticed in the latter units a phase modulation of the firing pattern by pauses occurring with a fixed periodicity of 2.5 to 10 s. Considered in the context of previous studies, these results strongly suggest an inhibitory influence of the raphe system on the olivo-cerebellar circuitry.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 48 (1982), S. 171-176 
    ISSN: 1432-1106
    Keywords: Raphe ; Cerebellum ; Harmaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of midbrain raphe stimulation and/or harmaline administration on cerebellar cell activities were examined in chloralosed rats. Cerebellar cortical cells were grouped into two categories. From a total sample of 68 cells, 48 were classified as Purkinje cells and the 20 others were unidentified. Midbrain raphe stimulation was found to inhibit for many sec the discharge of 40% of the Purkinje cells and 80% of the unidentified units. Other cells were unaffected, except 4 of them which were excited. Harmaline administration increased the CS firing rate of all Purkinje cells by inducing a rhythmic CS discharge at 7–12 Hz. Moreover, harmaline increased the discharge rate of unidentified units without inducing rhythmic activity. In both types of cerebellar cells a modulation of their firing pattern by periodical pauses at 0.1–0.4/s was noticed. These data are discussed in relation to the known influences of harmaline and cerebellar stimulation on raphe neurons. Taken in this context, results presented here confirm the existence of a modulatory influence of the raphe nuclei on the olivo-cerebellar circuitry. A general model of interactions is proposed.
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  • 6
    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.
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  • 7
    ISSN: 0942-0940
    Keywords: Adenoma ; morphometry ; prolactin ; pituitary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural morphometry was applied to 24 surgically removed human sparsely granulated prolactin cell adenomas in an attempt to correlate the measurements with blood prolactin levels, size of tumour, and age and sex of patient. No correlation was apparent. However, further evaluation revealed that correlation existed between size of tumour and blood prolactin levels, indicating that tumour mass, and not subcellular morphology, was related to the amount of prolactin released.
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  • 8
    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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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 36 (1981), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In a double-blind controlled trial 41 hospitalized adults with severe, perennial asthma of unknown aetiology were allocated to either an antigen-free elemental diet (Vivasorb®) or control diet, i.e. blended ordinary hospital food, for 2 weeks. At the time of entry into the trial all patients were in an active but stable phase of the disease. Medical treatment was given throughout the study as clinically indicated. Peak expiratory flow was measured hourly during the daytime and patients noted their symptoms daily on an assessment form. Validation of variables according to a scoring system indicated that the elemental diet resulted in an improvement of the patients' asthma (P 〈 0.05). It is concluded that elemental diet may serve as a diagnostic tool for disclosing alimentary intolerance in patients with perennial asthma.
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  • 10
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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