The influence of protein binding on the excretion of some sulphanilamidopyrimidines in man.

Abstract

Abstract The metabolism and excretion of sulphadimethoxine, sulphorthodimethoxine, sulphamethomidine, sulphasomidine and sulphadimethoxypyrimidine have been investigated in man. The plasma protein binding data including the percentage bound at various concentrations of the drugs, the number of binding sites (n), the binding capacity of plasma albumin (rmax) and the dissociation constant of the sulphonamide-albumin complex (K) for these compounds have been measured by ultrafiltration. The short-acting sulphasomidine is bound to a much lesser extent at the concentrations obtained clinically in the plasma than the long-acting drugs. Sulphasomidine occupies only one binding site on plasma albumin compared with the other sulphonamides investigated which occupy two sites. This may partly account for the rapid excretion of this compound in man. Sulphadimethoxine has two major metabolites, the N4-acetyl derivative and sulphadimethoxine-N1-glucuronide. N4-Acetyl sulphadimethoxine has similar binding constants to the parent compound. However the N1-glucuronide forms a weak complex with plasma albumin which has a lower binding capacity for this metabolite (rmax = 0.58) compared with sulphadimethoxine itself (rmax = 1.77). The results are discussed in relation to the excretion of these compounds.