Phenytoin Michaelis-Menten Pharmacokinetics in Caucasian Paediatric Patients

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Abstract
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 μg/ml for 0.5 to 3-year-old patients, 10.93 mg/kg/day and 6.82 μg/ml for the 4 to 6 year age group, 10.05 mg/kg/day and 6.51 μg/ml for the 7 to 9-year-olds, and 8.25 mg/kg/day and 5.69 μg/ml for the 10 to 16 year group. Using analysis of variance, the Vmax values were significantly different (p < 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 < 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 μg/ml. Because of these age-related pharmacokinetic differences, phenytoin dosages may require adjustment as paediatric patients become older.