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  • 1
    Digitale Medien
    Digitale Medien
    A dose-response study comparing suppression of plasma cortisol induced by fluticasone propionate from Diskhaler and budesonide from Turbuhaler (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 261-267 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Key words Fluticasone propionatei ; HPA-axis; bud esonide ; asthma ; children ; corticosteroids ; systemic effects ; plasma cortisol suppression
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Objective: To compare the systemic potency of inhaled fluticasone propionate delivered via Diskhaler® (FP-DH), and inhaled budesonide delivered via Turbuhaler® (BUD-TBH) over the clinically recommended dose range using plasma cortisol suppression as a marker for systemic activity. Methods: The systemic potency was examined in a dose-response study in 81 healthy male volunteers. The study was of an open, randomized, parallel-group (four groups) design, where two treatments were given in crossover fashion within each group. FP-DH and BUD-TBH were given b.i.d. for 7 days (14 doses): 100 and 100 μg (group 1); 200 and 200 μg (group 2); 500 and 400 μg (group 3); 1000 and 800 μg (group 4). There was a washout period of 7 days within each treatment group. All doses were administered at 08:00 and 20:00 hours. Multiple plasma cortisol samples were taken every 2 h over 24-h periods prior to randomization (baseline) and during steady state (i.e., the last two dosing intervals). Cortisol suppression was determined by comparing average plasma concentrations of cortisol before and during treatment. Dose-response curves for cortisol suppression were analyzed using multivariate non-linear regression (Hill modeling). Results: Multiple dosing for 7 days with FP-DH and BUD-TBH resulted in dose-dependent cortisol suppression by both drugs, most pronounced at the two highest dose levels. FP-DH-induced suppression was 41% at 500 μg and 86% at 1000 μg b.i.d., while that induced by BUD-TBH was 19% at 400 μg and 47% at 800 μg b.i.d. Statistically significant differences were found when comparing the two steroids at these two dose levels. Doses producing 50% of maximum suppression (ED50) were estimated at 833 μg b.i.d. for BUD-TBH and 479 μg b.i.d. for FP-DH. This gave an estimated relative cortisol suppression over the dose range of 1.74:1 (FP-DH:BUD-TBH). ED50 values, estimated from cortisol concentrations at 08:00 hours (12 h after the last dose), were 1212 μg b.i.d. for BUD-TBH and 527 μg b.i.d. for FP-DH giving a relative cortisol suppression of 2.30:1 (FP-DH:BUD-TBH). Fourteen subjects on the highest FP-DH dose and 3 at the next highest dose had morning plasma cortisol levels below the lower reference limit. No subject taking budesonide, however, had morning plasma cortisol levels below the reference limit. Analysis of the time for return to pretreatment baseline levels showed that cortisol suppression, 12–24 h after the last dose, was statistically significant compared with the baseline for the highest dose of FP-DH but not for any of the BUD-TBH doses. Conclusions: The results of the present study show that FP-DH suppresses plasma cortisol more than BUD-TBH on a equivalent basis with regard to both magnitude and duration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002280050287
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  • 2
    Digitale Medien
    Digitale Medien
    The rheological properties of AgI and Li2SO4 solid electrolytes, II. (1981)
    Springer
    Rheologica acta 20 (1981), S. 360-369 
    Details
    ISSN: 1435-1528
    Schlagwort(e): AgI ; Li2SO4 ; order-disorder transition ; plastic deformation ; superionic conductor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Physik
    Beschreibung / Inhaltsverzeichnis: Zusammenfasssung Die plastische Deformierbarkeit der superionischen Leiter AgI, Li2SO4 und an Li2SO4 reichen Li2SO4−K2SO4-Mischungen wurde durch Anwendung der Spannungsrelaxation untersucht. Das gemessene Aktivierungsvolumen ist umgekehrt proportional zur effektiven Anfangsspannung, doch ist die Proportionalitätskonstante kleiner als bei normalen Substanzen. Diese Tatsache kann mit der schwachen räumlichen Hemmung der Rotation der Gittereinheiten in Zusammenhang gebracht werden, die kennzeichnend für Rotationsphasen ist. Diese bilden daher eine weitere Ausnahme bezüglich der allgemeinen empirischen Relation, wie sie von Kubát und Mitarbeitern entdeckt worden ist. Das Vorhandensein eines „order-disorder“-Überganges in AgI in der Nähe von 700 K wird sowohl durch die Spannungsrelaxations-Messungen als auch durch die Auftragung von Maximumwerten der Schubspannung gegen die der Schergeschwindigkeit bestätigt. Bei der doppelt-logarithmischen Auftragung der letztgenannten Werte läßt sich die Änderung der Fließeigenschaften unmittelbar ablesen.
    Notizen: Summary The plastic deformation of the superionic conductors AgI, Li2SO4, and Li2SO4−K2SO4 mixtures rich in Li2SO4 has been investigated using stress relaxation. The observed activation volume is inversely proportional to the effective initial stress, but the proportionality constant is smaller than in “normal” non-superionic substances. This fact can be attributed to the weak steric hindrance for rotation of the lattice units, making the rotatorphases into an additional exception to the general empirical relation found by Kubát and coworkers. The existence of an order-disorder transition in AgI close to 700 K is confirmed by the stress relaxation data and also by measurements of maximum shear stress versus maximum shearing rate. It is found that such data may be conveniently represented by doubly logarithmic plots, in which a change in flow properties can be easily spotted.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01547667
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