Transformation and Excretion of Drugs in Biological Systems. VIII. Interactions between 5-n-Butyl-1-cyclohexyl-2, 4, 6-trioxoperhydro-pyrimidine and Sulfonamides in Dogs

Interaction between 5-n-butyl-1-cyclohexyl-2, 4, 6-trioxoperhydropyrimidine (BCP), which is one of non-steroidal anti-inflammatory agents, and several sulfonamides was investigated in dogs. Decline of plasma level of sulfamethizole, sulfamethizole-N4-acetate and sulfisomezole-N4-acetate was retarded by simultaneous medication of BCP. By simultaneous medication of BCP, sulfisomezole caused a small sudden drop of plasma level, but no alteration was observed with sulfanilamide. BCP possesses strong displacing activity for binding of certain sulfonamides to dog plasma proteins. The clearance ratios of sulfamethizole, sulfamethizole-N4-acetate and sulfisomezole-N4-acetate were remarkably decreased after BCP infusion. No significant alteration of the clearance ratio of sulfisomezole and sulfanilamide was observed. The clearance ratio of BCP was very low when the urine pH is below 8, but increased in metabolic alkalosis. The renal excretion of BCP was significantly blocked by iodopyracet infusion indicating that BCP is secreted through the proximal tubular route by the PAH transport mechanism. It became clear that prolongations of plasma levels of the certain sulfonamides by BCP, are mainly due to competitive interactions between the certain sulfonamides and BCP at renal secretory level.