Displacement from protein binding of sulphormethoxine by phenylbutazone using in vivo dialysis in rats

Abstract

Displacement of the ultra‐long‐acting sulphonamide sulphormethoxine from binding to serum proteins by phenylbutazone has been demonstrated by in vivo dialysis in rats. The technique used involved the introduction of dialysis sacs into the peritoneal cavity. The regression line relating free to total sulphormethoxine was significantly displaced after addition of phenylbutazone to the regime although the mean level of free drug was not significantly raised. No significant effect was observed on the proportion of phenylbutazone in the free form. The range of concentrations employed corresponded to that encountered clinically. In vitro experiments with comparable concentrations of both drugs confirmed displacement of sulphormethoxine by phenylbutazone. Insignificant displacement of phenylbutazone from binding occurred. These experiments indicated the relationships between the relative affinities of sulphormethoxine and phenylbutazone for serum proteins and the extent to which mutual displacement from binding occurred.

Effect of ACTH, corticoids and PCN (pregnenolone-16α-carbonitrile) on drug responses and disposition

“…Zoxazolamine (in 0.2 ml of acidified distilled water) was added to this pool· in aliquot quantities of total drug found in the plasma (first experiment, TABLE 28) of the corresponding groups. A shaking incubator was utilized at 37°C for 24 hr according to McQueen (1968McQueen ( , 1969, but equilibrium is established in vitro between the drug concentrations in plasma and in the sacs already after 2-3 hours.…”

Drug displacement from protein binding: isolation of a redistributional drug interaction in vivo

“…These studies were extended by McQueen (1969) who demonstrated, using in vivo dialysis in rats, the concomitant rise in free sulphonamide in the extracellular fluid when a displacing agent (phenylbutazone) was injected. Because of the small size of the rat, only one observation could be made on each animal after the injection of the displacing drug, and so the time course of the interaction could not be followed in a single animal.…”