Phenytoin Michaelis-Menten pharmacokinetics in Caucasian paediatric patients

The Michaelis-Menten pharmacokinetic parameters Vmax and Km were calculated for 135 epileptic paediatric patients receiving phenytoin as their only anticonvulsant therapy. Mean Vmax and Km values were 13.95 mg/kg/day and 6.59 micrograms/ml for 0.5 to 3-year-old patients, 10.93 mg/kg/day and 6.82 micrograms/ml for the 4 to 6 year age group, 10.05 mg/kg/day and 6.51 micrograms/ml for the 7 to 9-year-olds, and 8.25 mg/kg/day and 5.69 micrograms/ml for the 10 to 16 year group. Using analysis of variance, the Vmax values were significantly different (p less than 0.01) but the Km values were not. Linear regression analysis of Vmax versus age revealed a significant decline in Vmax with age (r = -0.554; p less than 0.001). A plot of Km versus age showed a poor correlation (r = -0.170) and a large amount of variability. Based on this data, the youngest age group would require on average 62% more phenytoin/kg/day than the oldest age group in order to maintain a steady-state phenytoin concentration of 15 micrograms/ml. Because of these age-related pharmacokinetic differences, phenytoin dosages may require adjustment as paediatric patients become older.