Phenytoin therapeutic drug monitoring for patients at Prasat Neurological Institute

Abstract

The subjects participated in this study were fifty four epileptic patients treated with phenytoin at Prasat Neurological Institute, 15 patients (27.78%) were treated with phenytoin alone and 39 (72.22%) were treated with phenytoin together with other antiepileptic drugs (phenobarbital, carbamazepine, valproic acid, clonazepam). The most common antiepileptics drugs used together with phenytoin was phenobarbital (42.59%). Percentabe of patients showed no beneficial effect from the drug were 24.24%. Percentage of patients showed central nervous system drug reaction was 52.31% while percentage of patient showed general adverse drug reaction was 39.40%. The incidence of phenytoin adverse reactions (general and CNS. Side effects) in the group of patients treated with phenytoin together with other antiepileptic drugs occurred more often (46.00%) than in the group of patients treated with phenytoin alone (20.00%). The general adverse drug reactions occurred most often was gum hypertrophy (31.82%) which occurred equally often in every range of phenytoin concentrations but the frequency of occurrence tends to related to the duration of phenytoin used. Nystagmus was the central nervous system adverse drug reactions found most often and the frequency of occurrence was related to the serum concentration of phenytoin. Fourty three patients (79.63%) did not require phenytoin dosage regimen adjustment while eleven patients (20.37%) did. After dosage adjustment 83.33% showed improvement in seizure control while 100.00% showed decrease in adverse reaction. The difference between measured and predicted values of phenytoin serum concentration was great since the population parameters were used in the calculation process, the mean percentage of difference between measured and predicted values was 129.81±293.15 (mean±SD). Km ranged from 1.34 to 45.18 mg/kg/d and Vmax ranged from 6.34 to 13.58 ug/mL. When only one dose and its corresponding serum concentration were known, the method which fix Km to be equal to 4, while calculating Vmax of the individual patient was recommended to be the method of choice. When two doses and their corresponding serum concentrations were known, the patient individual pharmacokinetic parameters could then be calculated, the prediction of phenytoin serum concentration showed tendency to be most accurate.