We reviewed our data from 122 records of patients taking phenytoin for the treatment of various types of epilepsy and selected 15 (age range 10-43 years old) who were on phenytoin alone to calculate Michaelis-Menten pharmacokinetic parameters. The average Vm and Km for this age group was found to be 8.45 mg/kg/day and 6.72 mg/litre, respectively. Km was independent of age and weight. Vm correlated well with weight but there was no relationship with age.
We estimated individual and population Michaelis-Menten pharmacokinetic parameters for phenytoin (DPH) in epileptic patients attending our neurology clinic using the computer programme. OPT. Our results agreed well with literature values but were lower than those we obtained earlier in a smaller number of patients. The Km was independent of age, weight and sex but there was a weak, correlation between Vm and body weight. We conclude that the use of population Vm and Km in normograms could lead to errors in DPH dose estimations as they correlated very poorly with patient characteristics. OPT was easy to use and sufficiently accurate for deriving dose estimates in routine patients. Its use would enable practitioners to generate their patients' own parameters for use in individual dosage adjustments. The estimates can subsequently be updated as more data become available.
The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown.