Charcoal hemoperfusion in the treatment of phenytoin overdose

In the case of phenytoin, a drug that is generally highly protein bound, th ere is a lack of consensus on the use of charcoal hemoperfusion in cases of overdose. We performed charcoal hemoperfusion on a phenytoin-overdosed pat ient to assess the effectiveness of this treatment. The plasma concentratio ns of total and free phenytoin fell rapidly, from 40.0 mu g/mL and 3.6 mu g /mL to 16.2 mu g/mL and 1.5 mu g/mL, respectively, after 3 hours of hemoper fusion, The total phenytoin elimination half-life was 3.9 hours. The fracti on of protein-bound phenytoin was constant (90.8% +/- 0.5%) before, during, and after the procedure. The relations between the in vitro protein bindin g and adsorption of phenytoin to activated charcoal were also examined. Int erestingly, bound phenytoin was found to dissociate from plasma proteins in the presence of activated charcoal and subsequently became adsorbed to the activated charcoal. Considering that phenytoin is bound to albumin with a large number of binding sites (n = 6) and a small binding constant (K = 6 x 10(3)/mol/L), the extent of adsorption to activated charcoal may depend on the magnitude of the binding constant of the drug to plasma proteins. The current results suggest that charcoal hemoperfusion is effective for the re moval of drugs that bind to plasma proteins with a low binding constant. (C ) 2000 by the National Kidney Foundation, Inc.