As serum concentration of phenytoin rises, particularly above 15mg/l, the metabolism slows substantially. This is called 'zero order kinetics'. At levels below 15 mg/l, doubling the dose will lead to doubling of serum concentration and the half life is 24 hrs. As metabolism slows at higher concentrations, even a 50 mg change in dose can double the serum concentration, and the half life increases to 48-70 hrs.Since the half life is so prolonged, a steady state after dose adjustments may not occur for weeks, with serum levels slowly rising over this time. This can easily lead to serious phenytoin toxicity.
Ref : Therapeutic Strategies in Epilepsy ( French and Delanty)
Ref : Therapeutic Strategies in Epilepsy ( French and Delanty)
