Assessment of the nephrotoxic potential of ceftazidime and a ceftazidime/tobramycin combination in volunteers.

Ten informed healthy volunteers with normal renal function received 2 X 3.0 g ceftazidime intravenously for three consecutive days. Four weeks later, ceftazidime was combined with 1 X 3 mg/kg body weight tobramycin, administered intramuscularly, for three consecutive days. The effect of the two treatments on parameters used to assess renal function was examined prior to administration, during administration for three days and for a follow-up period. Alanine-aminopeptidase (AAP) levels in 24 h urine samples were measured in addition to kidney function parameters. The urine from the volunteer who had shown the highest AAP levels in each series was examined by ultracentrifugation for the presence of membrane particles with AAP activity. Ceftazidime showed no effect on the proximal tubular membrane. No increased elimination of AAP could be demonstrated. The kidney function parameters remained unchanged. The combination of ceftazidime with tobramycin led to a cumulative increase in AAP activity which was not significantly different from the increase observed when the same dose of tobramycin is administered alone. No additive effects could be demonstrated. Ultracentrifugation showed no indication of an impairment of the membrane integrity when ceftazidime was administered alone or in combination with tobramycin.