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The pharmacokinetics of fosfomycin, an original antimicrobial agent, were investigated in 11 voluntary hemodialyzed patients. Fosfomycin, 2 g, was administered intravenously, 15 minutes before hemodialysis began in group 1 (6 patients), and just after hemodialysis in group 2 (6 patients). Blood samples were collected during 8 hours (group 1) and during 44 hours (group 2). Antibiotic concentrations were determined microbiologically. In group 1, half-life was 4.2 +/- 0.27 hours, total clearance 65.1 +/- 7.1 ml/mn and clearance by hemodialyzer 103 +/- 10 ml/mn. In group 2 plasma levels were 60 mg/l at the 44th hour and half-life was 48.8 +/- 17.5 hours. These results suggest that fosfomycin is actively eliminated by the hemodialyzer in group 1, and largely retained between two dialysis sessions in group 2. As for therapy, intravenous administration of 2 g after dialysis and further administration after each succeeding session are proposed.

Kinetics of fosfomycin were investigated in six patients undergoing continuous ambulatory peritoneal dialysis. Each subject received both an i.v. and an i.p. 1 g dose of fosfomycin with a one week washout between doses. Fosfomycin was assayed by a microbiological diffusion technique. After intravenous injection the fosfomycin serum kinetic parameters were as followed: elimination half-life (t1/2 beta) 38.4 +/- 8.7 h; volume of distribution 0.32 +/- 0.02 l/kg; total plasma clearance 7.0 +/- 1.4 ml/min and peritoneal clearance 3.2 +/- 0.2 ml/min. Dialyzate fosfomycin concentrations reached a maximum mean value of 32.2 +/- 2.8 micrograms/ml at 4 h post-injection and fosfomycin was detectable in dialyzate samples for up to 72 hours post-dosing. After intraperitoneal instillation, fosfomycin appeared in the serum rapidly and the mean peak plasma concentration was 36.2 +/- 2.8 micrograms/ml at the 4th h. The absorption rate (ka) was 0.580 +/- 0.039 h-1 and the absorption of fosfomycin from peritoneal space was 68.4 +/- 6.0%. These data suggest a bidirectional exchange through the peritoneal membrane. Intraperitoneal administration of 1 g either 48 h apart for anephric patients or 36 h apart for patients with residual renal function may achieve therapeutic serum concentrations.