Pharmacokinetic study of cefodizime in experimentally infected animals

Cefodizime, a new cephem antibiotic, was intravenously injected to mice with systemic or urinary tract infection by Escherichia coli and those with respiratory infection by Streptococcus pneumoniae, and the time courses of the plasma and tissue cefodizime levels were determined and compared with those in healthy mice (control group). In mice with systemic infection, the drug level in the plasma, liver, kidneys and lung changed on the basis of the two-compartment model. In this group, disappearance of the drug from plasma and tissues was obviously delayed and decrease in elimination constant (KE) and increase in the apparent volume of distribution (V2) were noted as compared with the control group. In the group with respiratory infection, T1/2(beta) and AUC for the hepatic drug level and T1/2(beta) for the renal drug level increased but in the other organs there was no great difference from the control group. In the urinary tract infection group, T1/2(beta) and AUC in the kidneys (infected site) and liver that mainly participate in elimination of cefodizime considerably increased differently from the control group. Changes of the distribution volume seemed to correspond with a physiological change of increase in body water content in the peripheral tissues (muscle, etc.) of the systemic infection group and in the liver, kidneys, etc. of the urinary tract infection group. Regarding the protein binding ratio, the urinary tract infection group showed a significant decrease as compared with the control group, but no distinct difference was noted in systemic and respiratory infections.