Apparent Michaelis-Menten kinetic parameters of phenytoin in pediatric patients.
In a retrospective study of 104 pediatric patients (0.5-16 yr) with seizures, the effects of concurrently administered anticonvulsants on Michaelis-Menten kinetic parameters of phenytoin were investigated. Individual kinetic parameters (Km and Vmax) for phenytoin were estimated from at least two reliable steady-state plasma concentration and dose data. Km tended to increase and to become more variable as the number of coadministered anticonvulsants increased. Significant difference was found in a group of patients taking three or more coadministered anticonvulsants. On the contrary, Vmax was not affected by those drugs in the higher age groups. Additive inhibitory rather than inductive effects of commonly used anticonvulsants appeared likely to cause an increase in Km. These observations suggest that dosage regimen adjustment of phenytoin based on the averaged Vmax in a given pediatric age group rather than the Km is recommended for a particular patient with inadequate therapeutic control of seizure or toxicity of this drug.