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  • 1995-1999  (2)
  • Cardiovascular effects; pharma-cokinetics  (1)
  • Perovskite  (1)
  • Acquired immune deficiency syndrome
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  • 1
    ISSN: 1432-1041
    Keywords: Key words Nebivolol ; Cardiovascular effects; pharma-cokinetics ; healthy volunteers ; obese subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of a single i.v. dose of the new racemic β-adrenoceptor-blocker nebivolol [0.073 mg base · kg–1 ideal body weight (IBW)] was studied in 9 obese (157% IBW) and 9 non-obese healthy volunteers (98% IBW). Each group contained 4 men and 5 women, aged 32 years, including one poor hydroxylator (dextrometorphan test). Methods: The cardiovascular effects of nebivolol are significant decreases in systolic and diastolic blood pressure, heart rate and cardiac output, which last up to 4–5 h. The plasma concentrations of the separate d- and l- enantiomers of nebivolol, with and without hydroxylated metabolite, were measured by radioimmunoassay and the unchanged racemate by high-pressure liquid chromatography (HPLC). The pharmacokinetic parameters for each form were calculated separately. Results: The main pharmacokinetic parameters of unchanged nebivolol in extensive metabolizers were (controls): distribution volume at steady state (Vss) 673 l; volume corrected by real body weight (Vss · kg–1) 11.2 l ·  kg–1; total clearance (CL) 51.6 h–1; and terminal half-life (t1/2) 10.3 h. The Vss (898 l) and CL (71.6 l · h–1) were significantly higher in obese patients. But Vss · kg–1 (9.4 l · kg–1) and t1/2 (10.0 h) were not significantly different from those in controls. The CL was clearly reduced (15–18 l · h–1) and the t1/2 prolonged (32–34 h) in poor hydroxylators, in both control and obese subjects. The pharmacokinetic parameters of the separate unchanged enantiomers were similar to those of the racemate in both groups. The pharmacokinetics of l-nebivolol were more influenced by the hydroxylation phenotype than those of d-nebivolol. The trend of the results for the sum of each enantiomer plus its metabolite, was similar to those for the unchanged form. Conclusion: The distribution of nebivolol in the adipose tissue in obese subjects is limited, despite its high lipophilicity. The differences between obese and non-obese subjects were not clinically relevant.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Physics and chemistry of minerals 27 (1999), S. 81-87 
    ISSN: 1432-2021
    Keywords: Key words Electrical conductivity ; Polarons ; Hopping ; Pressure ; Lower mantle ; Perovskite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Abstract Electrical conductivity of the lower mantle-like assemblage (Mg,Fe)SiO3 perovskite-(Mg,Fe)O magnesiowüstite is usually analyzed using the quasi-chemical Arrhenian approach of diffusion. The conductivity of this assemblage has often been attributed to hopping of small polarons, because of the low value of the activation energy and the small negative activation volume. However, the solid-state physics approach can provide more arguments, for or against conduction by polarons. We have tried to bridge the gap between the two approaches and identify the physical quantities entering the phenomenological activation parameters. In particular, we have investigated the pressure dependence of the activation energy, and the physical meaning of the activation volume. Hopping is controlled by the binding energy of the polaron and by the value of the exchange integral, which increases with pressure causing the observed decrease of the activation energy. From the physical theory and the results of experiments at pressures up to 40 GPa and temperatures up to 400 ∘C, we have estimated the values of parameters characteristic of polarons: radius, mobility, time between jumps and adiabaticity. These values are compatible with conduction by small adiabatic polarons. The consequences for extrapolations to lower mantle conditions of the presence of a temperature dependent preexponential term in the expression for conductivity have been examined. It was found that the extrapolations are not significantly different from those using the Arrhenius equation.
    Type of Medium: Electronic Resource
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