Use of multi-dose activated charcoal in phenytoin toxicity secondary to genetic polymorphism

Abstract

Introduction. Phenytoin is metabolised in the liver by cytochrome (CYP)2C9 and 2C19 enzymes. Due to saturation of enzyme capacity, the elimination half-life is prolonged at supratherapeutic levels. Genetic polymorphisms of CYP2C9 and 2C19 are reasonably common and further prolong the elimination of phenytoin. There are conflicting reports regarding whether multiple-dose activated charcoal (MDAC) significantly increases the clearance of phenytoin in poisoning. Case report. We present 3 patients with phenytoin toxicity and very slow elimination secondary to reduced CYP enzyme function from genetic polymorphisms. MDAC was used in two patients and led to rapid and large reductions in the measured elimination half-lives. This is contrasted with very prolonged elimination in a third patient who did not receive MDAC. Conclusion. MDAC may play a role in the management of chronic phenytoin toxicity, especially in those with very slow endogenous elimination secondary to genetic polymorphisms.

Keywords:

• Anticonvulsant
• Pharmaceuticals
• CNS
• Complications of poisoning
• Metabolic

Authors’ contributions

BC was responsible for the manuscript writing. NB gave advice on the figure and pharmacokinetic calculation of phenytoin from Prism Graphpad. All authors assisted in the editing of the final draft of the manuscript.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

There is no funding source for this report

Supplementary material available online

Supplementary Appendix 1.