How tightly can a drug be bound to a protein and still be removable by charcoal hemoperfusion in overdose cases?
BACKGROUND
Charcoal hemoperfusion is a very effective extracorporeal treatment in cases of drug overdose. The volume of distribution of a drug is the most important factor in limiting the efficacy of the treatment. Typically, drugs with a small volume of distribution are more efficiently removed by this treatment. In contrast, the effect of the plasma protein binding properties of drugs on their removal is not well understood, but it is clear that this binding percentage is an additional factor that affects the treatment.


OBJECTIVE
To clarify the role of protein binding of a drug on the effectiveness of charcoal hemoperfusion and to define a guideline for this treatment based on the percentage of drug binding.


METHODS
Twelve patients with drug overdoses involving 20 different (a total of 32) drugs were hemoperfused using a charcoal column at Japanese Red Cross Kumamoto Hospital in 2000. Immediately after the beginning of the treatment, the plasma concentrations of the drugs in the blood entering (A) and leaving (V) the charcoal column were determined. The extraction efficiency, (A-V)/A, of each drug was then calculated.


RESULTS
The efficacy of drug removal through adsorption to activated charcoal was found to be dependent on the binding affinity which is related to the protein binding percentage. The relationship between the extraction efficiencies of a charcoal column and the plasma protein binding percentages of the drug(s) showed that drugs that were bound at levels of 90-95%, or less, were effectively removed from the blood.


CONCLUSIONS
Charcoal hemoperfusion can effectively remove drugs with a protein binding percentage as high as 95%. In addition to the volume of distribution, the plasma protein binding percentage of the drug can be used as a determinant for clearance by hemoperfusion especially in cases of a drug that binds tightly to a protein.
Kawasaki
Chiyo I
CI
Department of Pharmacy, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan.
Nishi
Reiko
R
Uekihara
Souichi
S
Hayano
Syunichi
S
Kragh-Hansen
Ulrich
U
Kawasaki
Chiyo I
CI
Otagiri
Masaki
M
D000327:Adsorption; D002606:Charcoal / Q000737:chemistry / Q000627:therapeutic use*; D062787:Drug Overdose; D064420:Drug-Related Side Effects and Adverse Reactions; D006464:Hemoperfusion; D006801:Humans; D007564:Japan; D009961:Orosomucoid / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism*; D011041:Poisoning / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*
D009961:Orosomucoid; D004364:Pharmaceutical Preparations; D012709:Serum Albumin; D002606:Charcoal