PHARMACOKINETICS OF INTRAVENOUS AND INTRAPERITONEAL FOSFOMYCIN IN CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS

  • 1 January 1988
    • journal article
    • research article
    • Vol. 29  (1) , 35-40
Abstract
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 .mu.g/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 .mu.g/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.