title: Pharmacokinetics of intravenous and intraperitoneal fosfomycin in continuous ambulatory peritoneal dialysis.
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 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.
authors: Department of Clinical Nephrology, Pellegrin-Tripode Hospital, Bordeaux, France.
authors: J L
authors: JL
authors: Bouchet
authors: H
authors: H
authors: Albin
authors: C
authors: C
authors: Quentin
authors: B
authors: B
authors: de Barbeyrac
authors: G
authors: G
authors: Vinçon
authors: P
authors: P
authors: Martin-Dupont
authors: L
authors: L
authors: Potaux
authors: M
authors: M
authors: Aparicio
mesh_terms: D005260:Female; D005578:Fosfomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D013997:Time Factors
chemical_list: D005578:Fosfomycin