The disposition of cefazolin and tobramycin following intraperitoneal administration in patients on continuous ambulatory peritoneal dialysis

Two groups of patients with bacterial peritonitis were studied to examine the pharmacokinetics of intraperitoneal tobramycin and cefazolin. In Group 1, four patients received tobramycin (5 mg/l) and cefazolin (75 mg/l) in two litres of dialysate for 12 consecutive exchanges. In Group 2, five patients received a loading dose of tobramycin (50 mg/l) and cefazolin (500 mg/l) intraperitoneally in exchange one. In exchanges three through 12, the maintenance schedule was tobramycin (7.5 mg/l) and cefazolin (250 mg/l). Tobramycin was measured by EMIT and cefazolin (in Group 2 only) by HPLC. Serum and dialysate levels were determined at the end of each of 12 exchanges. In Group 1, steady-state tobramycin levels appeared in 48 hours in both serum and dialysate to levels of 2.1 ± 0.2 μg/ml (x ± SEM) and 2.5 ± 0.3 μg/ml respectively. In Group 2, the loading dose schedule provided levels in serum at the end of the first dwell for tobramycin of 4.3 ± 0.64 μg/ml and for cefazolin 54.8 ± 6.7 μg/ml. Steady state levels for tobramycin and cefazolin were 3.7 ± 0.15 μg/ml and 110.9 ± 8 μg/ml respectively. Concomitant dialysate levels for tobramycin were 3.9 ± 0.17 μg/ml and for cefazolin 80.6 ± 26 μg/ml. The total body clearance of tobramycin in both studies was about 6.2 ml/min. For cefazolin in Group 2, the total body clearance was 7.8 ml/min. The loading dose schedule is recommended for peritonitis when a rapid therapeutic serum level is required.