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Melphalan concentration dependent plasma protein binding in healthy humans and rats (1987)

Greig, N. H. ; Sweeney, D. J. ; Rapoport, S. I.

Springer

European journal of clinical pharmacology 32 (1987), S. 179-185

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ISSN: 1432-1041

Keywords: melphalan ; protein binding ; plasma ; humans ; rats ; pharmacokinetics

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary The binding of melphalan to plasma proteins from four healthy humans and from rats was measured by centrifugal ultrafiltration. Melphalan concentrations were determined by HPLC and by measuring 14C-melphalan activity. In whole blood, melphalan was distributed preferentially in plasma. However, a constant fraction, 37%, which was independent of the total melphalan concentration in whole blood, was present within the red blood cells. The binding of melphalan to plasma proteins from humans was less than that from rats. In both, however, the fraction bound was constant throughout the concentration range (0.1 to 9.0 µM) that is achieved during standard-dose melphalan therapy. Albumin was the primary binding protein. At concentrations equal to or in excess of 33 µM, which have been achieved during high-dose melphalan therapy, free plasma melphalan concentrations were no longer linearly related to total drug concentrations, and the plasma protein binding of melphalan in the human became concentration dependent. This occurred at concentrations of 70 µM in the rat. Scatchard analysis of the data indicated the presence of 2 groups of binding sites. Class I sites had 0.03 and 0.4 binding sites per albumin molecule in humans and rats, with respective association constants of 4.43 × 104M−1 and 1.92 × 104M−1. Class II sites had 5.18 and 2.60 binding sites per molecule, with repective association constants of 3.82 × 102M−1 and 2.01 × 102M−1.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00542192

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Thermal Expansion Kinetics: Method to Measure Permeability of Cementitious Materials, IV. Effect of Thermal Gradients and Viscoelasticity (2005)

Ciardullo, J. P. ; Sweeney, D. J. ; Scherer, G. W.

Oxford, UK : Blackwell Science Inc

Journal of the American Ceramic Society 88 (2005), S. 0

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ISSN: 1551-2916

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics

Notes: When a porous material that is saturated with liquid is heated, the liquid expands much more than the solid phase. If the permeability is low, then the liquid may not be able to escape as it expands, so it expands within the pores and causes dilatation of the body. In that case, by analyzing the kinetics of dilatation during a change in temperature, it is possible to extract the permeability. Previous papers have examined the behavior of an elastic or viscoelastic (VE) porous solid subjected to a thermal cycle slow enough to avoid internal temperature gradients. However, for cementitious samples, the sample size must be large enough that thermal gradients are likely. In this paper, we show that the effect of the gradient can be readily incorporated into the analysis of experimental data. For cement paste, experiments reveal that VE relaxation has a greater influence on the results than the gradient in temperature.