How tightly can a drug be bound to a protein and still be removable by charcoal hemoperfusion in overdose cases?

Chiyo Imamura, Reiko Nishi, Souichi Uekihara, Syunichi Hayano, Ulrich Kragh-Hansen, Masaki Otagiri

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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. Study Design and 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.

Original languageEnglish
Pages (from-to)95-99
Number of pages5
JournalJournal of Toxicology - Clinical Toxicology
Volume43
Issue number2
DOIs
Publication statusPublished - 2005
Externally publishedYes

Fingerprint

Hemoperfusion
Charcoal
Pharmaceutical Preparations
Protein Binding
Proteins
Drug Overdose
Blood Proteins
Blood
Therapeutics
Red Cross

Keywords

  • Charcoal hemoperfusion
  • Overdose
  • Protein binding

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

How tightly can a drug be bound to a protein and still be removable by charcoal hemoperfusion in overdose cases? / Imamura, Chiyo; Nishi, Reiko; Uekihara, Souichi; Hayano, Syunichi; Kragh-Hansen, Ulrich; Otagiri, Masaki.

In: Journal of Toxicology - Clinical Toxicology, Vol. 43, No. 2, 2005, p. 95-99.

Research output: Contribution to journalArticle

Imamura, Chiyo ; Nishi, Reiko ; Uekihara, Souichi ; Hayano, Syunichi ; Kragh-Hansen, Ulrich ; Otagiri, Masaki. / How tightly can a drug be bound to a protein and still be removable by charcoal hemoperfusion in overdose cases?. In: Journal of Toxicology - Clinical Toxicology. 2005 ; Vol. 43, No. 2. pp. 95-99.
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AB - 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. Study Design and 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.

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