Effect of simultaneous administration of drugs on absorption and excretion. 3. Effect of non-steroidal anti-inflammatory agents and sulfadimethoxine N4-acetate on antibacterial activity of sulfadimethoxine in vitro (author's transl)

Abstract

The inhibitory effect of non-steroidal anti-inflammatory agents on the binding of sulfadimethoxine (SDM) with bovine serum albumin (BSA) in vitro was determined by equilibrium dialysis method. The effect of non-steroidal anti-inflammatory agents on antibacterial activity of SDM in the presence of BSA was analyzed by thin-layer paper disc method and compared with the results obtained from the former. The effect of sulfadimethoxine N4-acetate, which is one metabolite of SDM, on the binding of SDM with BSA, and antibacterial activity of SDM in the presence of BSA was tested by the same method. These studies revealed the following : (1) The displacing activity of non-steroidal anti-inflammatory agents on the binding of SDM with BSA decreased in the order of phenylbutazone, salicylic acid, mefenamic acid, bucolome, indomethacin, and benzydamine. (2) Antibacterial activity of SDM was markedly reduced by the addition of BSA. (3) Antibacterial activity of SDM that decreased in the presence of BSA was recovered by the addition of non-steroidal anti-inflammatory agents. This activity decreased in the order of phenylbutazone, salicylic acid, bucolome, indomethacin, and benzydamine. (4) Sulfadimethoxine N4-acetate also inhibited the binding of SDM with BSA and increased this reduced antibacterial activity of SDM.