A DRUG-INDUCED CHANGE IN THE DISTRIBUTION AND RENAL EXCRETION OF SULFONAMIDES

¹ Departments of Psychiatry, and Pharmacology and Therapeutics, University of Florida, College of Medicine, Gainesville, Florida

The distribution of certain sulfonamides in the rat can be modified by interfering with their binding to plasma protein by another drug. Of a wide variety of drugs tested, sulfinpyrazone, ethyl biscoumacetate and iophenoxic acid were found to be the most active in displacing a sulfonamide from albumin. Effective displacing agents in this system were acidic and highly bound to plasma. Other desirable structural characteristics were suggested on the basis of the drugs found to be active.

The effect of the displacing agent in vivo appeared due to interference with the binding of the sulfonamide, since drugs active in vitro were the only ones active in vivo, and in the same relative order. The displacing agent altered the plasma and tissue concentrations only of those sulfonamides that showed more than 45% plasma binding.

The net effect of displacement in vivo was a drop in plasma concentration of total drug and an increase in the unbound fraction, resulting in an increased concentration of sulfonamide (unbound) in tissue.

The displacing agent used (sulfinpyrazone), being a strong organic acid (pKa 2.8) also competed for the renal secretion of those sulfonamides which were handled in this manner. The overall effect of sulfinpyrazone therefore was assessed on the basis of its effect on the kidney as well as its effect on plasma binding.

This article has been cited by other articles:

				A. H. Anton and R. E. Rodriguez Drug-Induced Change in the Distribution of Sulfonamides in the Mother Rat and Its Fetus Science, June 1, 1973; 180(4089): 974 - 976. [Abstract] [PDF]