ABSORPTION, DISTRIBUTION AND EXCRETION OF SULBACTAM AND CEFOPERAZONE AFTER PARENTERAL ADMINISTRATION TO EXPERIMENTAL ANIMALS

Abstract

Pharmacokinetics of the combination of sulbactam (SBT) and cefoperazone (CPZ) administered intravenously or subcutaneously to mice, rats and dogs were compared with those of SBT alone. The following results were obtained:
1) The serum levels of SBT and CPZ after intravenous administration of SBT/CPZ were higher in dogs than in rats. Their serum half lives were 20 and 21 minutes in rats, and 30-35 and 42-46 minutes in dogs, respectively. Serum levels of SBT and CPZ reached a peak 15 to 30 minutes after subcutaneous administration of the combination to mice, and then declined in parallel. The serum half lives of both drugs were about 20 minutes.
2) The tissue levels of drugs after intravenous administration of SBT/CPZ to rats were highest in the kidney, followed by the liver, serum and lung. After subcutaneous administration of SBT/CPZ to mice, SBT concentration was highest in the kidney, followed by the serum, lung and liver, and CPZ levels were highest in the liver, followed by the kidney, serum and lung in this order.
3) After intravenous administration of SBT/CPZ, SBT was predominantly recovered in the urine in mice, rats, and dogs. The urinary and fecal recoveries of CPZ were approximately 17% and 35% in rats, and 64% and 20% in dogs, respectively. Biliary recovery in rats was about 1% for SBT and about 54% for CPZ. Therefore, it seems that the major route of excretion for SBT was the urine and for CPZ the bile in rats and urine in dogs. The pharmacokinetics of SBT after administration of SBT alone were not different from those after administration of a combination of SBT/CPZ.
4) No active metabolite of SBT and CPZ was detected in rat urines by means of TLC-bioautography.
5) The extent of serum protein binding of SBT on coexisting of SBT and CPZ was about 20% for human and dog sera, 16% for rabbits and 56% for rats. That of CPZ was 77-93% in these animals.