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Protein-bound Compounds (protein-bound + compound)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Efficacy of peritoneal dialysis of tolbutamide in rats under conditions of the plasma unbound fraction being increased

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2009
Takashi Makita
Abstract Peritoneal dialysis of a highly protein-bound compound, tolbutamide, was examined in rats to clarify whether the efficacy of the peritoneal dialysis of such compounds increases proportionally as their unbound fractions increase. As expected, it was shown that the tolbutamide concentration of the peritoneal dialysate rose as the unbound fraction of tolbutamide increased. However, the efficacy of peritoneal dialysis of tolbutamide was proportionally elevated only when the unbound fraction was slightly increased by sulfamethoxazole treatment. When the unbound fraction of tolbutamide was increased 7.8 times by sulfadimethoxine treatment, the dialysis efficacy was increased to only 58% of that expected. This discrepancy between the observed and expected values regarding dialysis efficacy was more marked when experiments were performed in rats with experimentally induced acute renal failure. Pharmacokinetic analysis indicated that the intrinsic dialysis clearance of tolbutamide decreased when its unbound fraction was greatly increased. These findings suggest that peritoneal dialysis may be mediated not only by passive diffusion, but also by concentration-dependent processes. The efficacy of the peritoneal dialysis of therapeutic compounds may be overestimated if the estimation is based only on their unbound fraction measured under control conditions. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Enhancement of in vitro and in vivo microdialysis recovery of SB-265123 using Intralipid® and Encapsin® as perfusates

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2003
Keith W. Ward
Abstract This study was conducted to compare the ability of two potential microdialysis perfusates to enhance the recovery of SB-265123, a lipophilic, highly protein-bound compound, both in vitro and in vivo. Initial in vitro experiments established that the recovery of SB-265123 by microdialysis using normal saline as a perfusate was poor (1.7%). Different concentrations of Intralipid® and Encapsin® also were evaluated in an identical in vitro setting, to determine enhancement of recovery. In vitro recovery was enhanced to approximately 24 and 65% with 5 and 20% Intralipid®, and to approximately 59 and 62% with 5 and 20% Encapsin®, respectively. A rat in vivo study was conducted with 20% Encapsin® to confirm the in vitro observations. In the in vivo study, 75,80% recovery of free SB-265123 was achieved using 20% Encapsin® as a perfusate. The results from this study indicate that for SB-265123, a lipophilic, highly protein-bound molecule, Encapsin® is an efficient recovery enhancer in vitro. The results from this investigation further demonstrate that a recovery enhancer may be useful for in vivo applications, even with a compound that is highly bound to plasma protein. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Uremic Toxins: Removal with Different Therapies

HEMODIALYSIS INTERNATIONAL, Issue 2 2003
Raymond C. Vanholder
A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water-soluble compounds (<500 Da), protein-bound compounds, and middle molecules (>500 Da). The prototype of small water-soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water-soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra-dialytic behavior, which is different from that of urea. In addition, the protein-bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high-flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination. [source]

Prospective Evaluation of the Change of Predialysis Protein-Bound Uremic Solute Concentration With Postdilution Online Hemodiafiltration

ARTIFICIAL ORGANS, Issue 7 2010
Natalie Meert
Abstract Although protein-bound uremic compounds have been related to outcome in observational studies, few current dialysis strategies provide more removal of those compounds than standard hemodialysis. We evaluated the evolution of protein-bound uremic solutes after a switch from high-flux hemodialysis to postdilution hemodiafiltration (n = 13). We compared predialysis solute concentration at 4, 5, and 9 weeks versus baseline for several protein-bound compounds and water-soluble solutes, as well as for ,2 -microglobulin. After 9 weeks of postdilution hemodiafiltration, a significant decrease versus baseline could be detected for total concentration of protein-bound solutes: p-cresylsulfate (3.98 ± 1.51,3.17 ± 1.77 mg/dL, ,20%, P < 0.01) and 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid (0.72 ± 0.52,0.64 ± 0.46 mg/dL, ,11%, P < 0.01). For the other protein-bound solutes, hippuric acid, indoleacetic acid, and indoxylsulfate, no change in total concentration could be detected. The concentration of the middle molecule, ,2 -microglobulin, decreased as well after 9 weeks of postdilution hemodiafiltration (24.7 ± 9.3,18.1 ± 6.7 mg/L, ,27%, P < 0.01). For water-soluble compounds, no significant change of concentration was found. Postdilution hemodiafiltration in comparison to high-flux hemodialysis provided significant reduction of predialysis concentration of protein-bound compounds, especially those with the highest protein binding, and of ,2 -microglobulin, by ,11 to ,27% in 9 weeks. [source]