We studied the pharmacokinetics of a new cephem
antibiotic,
DQ-2556, in patients with impaired kidney function. The peak concentrations of the compound in the serum were observed irrespective of the degree of
kidney failure 5 minutes after its bolus administration of 1.0 g intravenously, and no significant difference was observed in the concentrations among the patients. On the other hand, the decrease in its concentrations in the serum was impeded in proportion to degrees of
kidney failure and, in particular,
hemodialysis patients showed markedly delayed clearance of the
drug from the serum; the half-lives in the serum (beta phase) were prolonged to ca. 6 hours in patients with severe
kidney failure (Ccr ca. 20 ml/min) and did so markedly to ca. 17 to 21 hours in patients with
hemodialysis as compared with ca. 2.5 hours in patients with slight
kidney failure (Ccr ca. 50 ml/min). Urinary excretion rates (0-to-24 hours values) were ca. 70% in patients with slight
kidney failure, ca. 60% in patients with moderate
kidney failure and ca. 40% in patients with severe
kidney failure, showing a tendency toward a decline in relation to increasing degrees of
kidney failure. The compound showed a satisfactory dialytic property. The clinical efficacy and safety of
DQ-2556 were evaluated upon administering if at daily doses of 0.5 g b.i.d. and 1.0 g b.i.d. for 7 and 14 consecutive days respectively, in patients with lower
respiratory tract infections. The clinical efficacies were excellent in 2 patients, good in 11 and poor in 2, yielding a efficacy rate of 86.7%. No side effects were observed, though, a neutrophil sedimentation ratio decreased in a patient, and a down-shift of
prothrombin activities was observed in another. These results suggest that
DQ-2556 is useful for lower
respiratory tract infections, but in patients with
kidney failures it is required to seek the most suitable regimen since the excretion rates of the compound decrease as degrees of
kidney failure become severer.