Biopharmaceutical studies on copper(II) chelates of sulfanilamide derivatives

Sulfanilamide유도체의 동(II)착화합물에 대한 생물약제학적 연구

Cu(II) chelates of several sulfanilamide derivatives (Sulfa-Cu) were prepared and their effects on solubility, absorptivity in intestinal lumen, biding tendency with serum protein and erythrocytes, concentration in rabbit blood, and acetylation rate were studied in comparison with their free ligand forms. For solubility concerned, the partition coefficients of Sulfa-Cu are decreased as following order: Sulfadimethoxine Copper chelate (SDM-Cu), Sulfamethoxypyridazine Copper chelate (SD-Cu), Sulfamerazine Copper chelate (SM-Cu), Sulfaisoxazole Copper chelate (SIX-Cu). The partition coefficients of SDM-Cu and ST-Cu were much greater than those of ligands. this phenomenone acounts for the rapid absorption of SDM-Cu and ST-Cu in the rat small intestine (in situ). The Sulfa-Cu were absorbed at the intestinal lumen of a rat in the rate of first order and there was no difference between long acting sulfa drugs and their Cu0chelates in biological half lives. In binding experiments, sulfa-Cu binded with serum protein in lower ratio than their ligands except SIX-Cu. On other hand, acetylation rates of sulfa-Cu were higher than those of free sulfa drugs and the acetylation rate were higher than those of free sulfa drugs and powder. In a experiment on Sulfa-Cu concentration in rabbit blood, the half lives of SD-Cu, SIX-cu, ST-Cu, and SM-Cu were longer than those of their ligands. Above all, the half life of SD-Cu appeared to be approximately 3.5 times logner than that of corresponding ligand, SD. When absorption of sulfa drugs or sulfa-Cu at the small intestinal lumen of a rat and the concentration in rabbit blood after absorption were compared, it was found that there was not always conrrelated.