Enhanced clearance of highly protein-bound drugs by albumin-supplemented dialysate during modeled continuous hemodialysis.
BACKGROUND
In 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.


METHODS
VPA, 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.


RESULTS
The 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.


CONCLUSIONS
Continuous 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.
Churchwell
Mariann D
MD
1Department of Pharmacy Practice, University of Toledo College of Pharmacy, Toledo, OH 43606-3360, USA. mariann.churchwell@utoledo.edu
Pasko
Deborah A
DA
Smoyer
William E
WE
Mueller
Bruce A
BA
D000418:Albumins / Q000008:administration & dosage*; D000818:Animals; D002220:Carbamazepine / Q000097:blood / Q000302:isolation & purification / Q000506:poisoning; D002417:Cattle; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood / Q000628:therapy; D015312:Hemodialysis Solutions / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010672:Phenytoin / Q000097:blood / Q000302:isolation & purification / Q000506:poisoning; D011041:Poisoning / Q000097:blood / Q000628:therapy*; D011485:Protein Binding; D006435:Renal Dialysis / Q000379:methods*; D014635:Valproic Acid / Q000097:blood / Q000302:isolation & purification / Q000506:poisoning
D000418:Albumins; D015312:Hemodialysis Solutions; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin