PREDICTION OF THE EFFECTIVENESS OF CHARCOAL HEMOPERFUSION TREATMENT IN DRUG OVERDOSE : A GUIDELINE BASED ON THE PROTEIN BINDING PERCENTAGE AND DISTRIBUTION VOLUME OF THE DRUG

Abstract

Charcoal hemoperfusion is a very effective treatment for removing drugs with a small volume of distribution in cases of overdoses. However, it is not capable of clearing generally high protein bound drugs. We successfully treated a phenytoin overdosed patient with charcoal hemoperfusion despite a relative high protein binding percentage (90.8 ± 0.5 %) was maintained before, during and after the procedure. In addition, we examined the in vitro protein binding of phenytoin in the presence of activated charcoal. The bound phenytoin was found to dissociate from plasma proteins and subsequently became adsorbed to the activated charcoal. There are two equilibria, one, an interaction between drug and activated charcoal and the other, an interaction between drug and plasma protein are competing processes. Considering that phenytoin is bound to albumin with a large number of binding sites (n=6) and a small binding constant (K = 6 × 10³ M^-1), the extent of adsorption to activated charcoal may depend on the magnitude of the binding constant of the drug to plasma proteins. Therefore, we measured the plasma concentrations of the drugs in arterial blood entering the charcoal column (A) from overdosed patients treated with charcoal hemoperfusion and those in venous blood exiting the column (V) to determine the extraction efficiency, (A-V)/A . Based on these results, we try to define a guideline for the treatment of drug overdose using the protein binding percentage and distribution volume of the drug.