Pharmacokinetics of intravenous and intraperitoneal fosfomycin in continuous ambulatory peritoneal dialysis

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.