AN EVALUATION ON PHARMACOKINETICS PARAMETERS OF PHENYTOIN IN ADULT EPILEPTIC PATIENTS: A SINGLE CENTRE STUDY FROM MALAYSIA

Phenytoin follows Michaelis-Menten, a non-linear pharmacokinetics that occurs when drug molecules saturates the enzymes ability to metabolise the drug. When this occurs, steady state phenytoin serum concentration increases in a disproportionate manner after a dosage increase. General population data are usually used for the phenytoin dose calculation. However, many studies show that population pharmacokinetic parameters of phenytoin have high variations. Thus, use of specific local pharmacokinetic parameters for each population group in estimating individualised phenytoin dose can reduce phenytoin toxicity cases. This prospective, observational study was conducted to estimate a local V_max and K_m of phenytoin for adult epileptic patients in neurological ward and clinic at Hospital Pulau Pinang, Malaysia. All therapeutic drug monitoring of oral capsule phenytoin were studied in a three-month data collection period. Out of the 17 subjects in our study, there are 13 male subjects (76.47%) and 4 female subjects (23.53%). A total 11 Malay subjects (64.71%), 4 Chinese subjects (23.53%) and 2 Indian subjects (11.76%) were included. Median V_max and K_m were found to be 8.25 mg/kg/day and 3.80 mg/l. Male subjects have a higher V_max (8.30 mg/kg/day) but a lower K_m (3.3 mg/l). Chinese population has the highest V_max (8.80 mg/kg/day). For K_m, Indian population is the highest, with a value of 5.5 mg/l. From our study, gender does not correlate with V_max and K_m of phenytoin (p-value 0.05). Ethnicity was also found to have no association with V_max and K_m (p-value 0.05). LocalV_max (8.25 mg/kg/day) is higher and K_m (3.8 mg/l) is lower when compared with standard V_max (7 mg/kg/day) and K_m (4 mg/l) obtained from Caucasian population.