• Mariann D Churchwell, Deborah A Pasko, William E Smoyer, and Bruce A Mueller.
• 1Department of Pharmacy Practice, University of Toledo College of Pharmacy, Toledo, OH 43606-3360, USA. mariann.churchwell@utoledo.edu
• Nephrol. Dial. Transplant. 2009 Jan 1; 24 (1): 231-8.

BackgroundIn 2006, there were 16 796 toxic exposures attributed to valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) reported to the US Toxic Exposure Surveillance System. Of these, 30% (5046) were treated in a health care facility with 12 cases resulting in death. These drugs are highly protein bound and poorly dialyzable; however, it has been suggested that albumin-supplemented dialysate may enhance dialytic clearance. We investigated whether the addition of albumin to dialysate affects dialytic clearance of VPA, CBZ and PHT.MethodsVPA, CBZ and PHT were added to a bovine blood-based in vitro continuous hemodialysis circuit, which included a polysulfone or an AN69 hemodialyzer. VPA, CBZ and PHT clearances were calculated from spent dialysate and pre-dialyzer plasma concentrations. VPA, CBZ and PHT clearances with control (albumin-free) dialysate were compared to clearances achieved with 2.5% or 5% human albumin-containing dialysate. The influences of blood flow (180 and 270 mL/min) and dialysate flow (1, 2 and 4 L/h) on dialysis clearance were also assessed.ResultsThe addition of 2.5% albumin to dialysate significantly enhanced dialytic clearance of VPA and CBZ, but not PHT. Use of 5% albumin dialysate further increased VPA and CBZ clearance. Overall, drug clearance was related directly to dialysate flow but independent of blood flow.ConclusionContinuous hemodialysis with albumin-supplemented dialysate significantly enhanced VPA and CBZ, but not PHT, clearance compared to control dialysate. Continuous hemodialysis with albumin-supplemented dialysate may be a promising therapy to enhance dialytic clearance of selected highly protein-bound drugs.

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