In vitro @entity8606 and @entity2264 membrane permeability to XXXX and in vivo pharmacokinetics during continuous renal replacement therapies.

@entity1 @entity8 @entity2264 @entity880 @entity8606 @entity5505
BACKGROUND: @entity5505 is a third-generation cephalosporin almost entirely eliminated by glomerular filtration and dose reductions are essential in @entity1 with @entity8 . The physicochemical and pharmacokinetic properties of @entity5505 make it susceptible to be eliminated by continuous renal replacement therapies (CRRT), but there is little clinical information to guide the correct administration in @entity1 undergoing these techniques. METHODS: In vitro procedures were carried out in three different fluids, using @entity8606 or @entity2264 membranes. Four @entity1 entered the in vivo study. Two @entity1 received 1,000 mg every 6 h and the other two 2,000 mg every 6 h. Concentrations of @entity5505 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 @entity880 was used as @entity5505 vehicle, but were lower in plasma samples (p < 0.05). In @entity1 , the Sc-Sa was 0.93 +/- 0.06 and correlated well with the unbound fraction (0.86 +/- 0.08). The contribution of CRRT to @entity5505 clearance was higher in anuric @entity1 than in nonanuric @entity1 . 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 @entity5505 every 6 h could be associated with unnecessarily high trough levels which increase the risk of drug nephrotoxicity. Nonanuric @entity1 undergoing CRRT need higher @entity5505 doses to reach adequate plasma concentrations against pathogens isolated in the critically ill.
