title: In vitro AN69 and polysulphone membrane permeability to ceftazidime and in vivo pharmacokinetics during continuous renal replacement therapies.
abstract: BACKGROUND
  Ceftazidime is a third-generation cephalosporin almost entirely eliminated by glomerular filtration and dose reductions are essential in patients with renal impairment. The physicochemical and pharmacokinetic properties of ceftazidime make it susceptible to be eliminated by continuous renal replacement therapies (CRRT), but there is little clinical information to guide the correct administration in patients undergoing these techniques.
  
  
  METHODS
  In vitro procedures were carried out in three different fluids, using AN69 or polysulphone membranes. Four patients entered the in vivo study. Two patients received 1,000 mg every 6 h and the other two 2,000 mg every 6 h. Concentrations of ceftazidime were measured by high-performance liquid chromatography.
  
  
  RESULTS
  No differences were detected in thesieving coefficients (Sc) or saturation coefficients (Sa)between membranes during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHD). Sc-Sa values were close to 1 when Ringer's lactate was used as ceftazidime vehicle, but were lower in plasma samples (p < 0.05). In patients, the Sc-Sa was 0.93 +/- 0.06 and correlated well with the unbound fraction (0.86 +/- 0.08). The contribution of CRRT to ceftazidime clearance was higher in anuric patients than in nonanuric patients.
  
  
  CONCLUSIONS
  No differences were shown in vitro in the Sc obtained with both membranes during CVVH or the Sa obtained during CVVHD. The contribution of clearance by CRRT to total clearance is clearly dependent on the renal function. The administration of ceftazidime every 6 h could be associated with unnecessarily high trough levels which increase the risk of drug nephrotoxicity. Nonanuric patients undergoing CRRT need higher ceftazidime doses to reach adequate plasma concentrations against pathogens isolated in the critically ill.
authors.affiliation: Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria-Gasteiz, Spain.
authors.forename: Arantxazu
authors.initials: A
authors.lastname: Isla
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Gascón
authors.forename: Javier
authors.initials: J
authors.lastname: Maynar
authors.forename: Alazne
authors.initials: A
authors.lastname: Arzuaga
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Sánchez-Izquierdo
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000180:Acrylic Resins; D000181:Acrylonitrile / Q000031:analogs & derivatives*; D000328:Adult; D000418:Albumins; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002442:Ceftazidime / Q000493:pharmacokinetics*; D017583:Hemodiafiltration; D006440:Hemofiltration; D006801:Humans; D007552:Isotonic Solutions; D007674:Kidney Diseases / Q000378:metabolism / Q000628:therapy; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D010539:Permeability; D010949:Plasma; D011108:Polymers; D000077325:Ringer's Lactate; D013450:Sulfones
chemical_list: D000180:Acrylic Resins; D000418:Albumins; D000900:Anti-Bacterial Agents; D007552:Isotonic Solutions; D008567:Membranes, Artificial; D011108:Polymers; D000077325:Ringer's Lactate; D013450:Sulfones; C017662:polysulfone P 1700; C016892:AN-69; D002442:Ceftazidime; D000181:Acrylonitrile