ABSTRACT
Phenytoin and phenobarbital steady-state concentrations in serum were measured by high-performance liquid chromatography according to our modification of the Soldin-Gilbert method. The well-known nonlinear, individually variable pharmacokinetics and narrow therapeutic index of phenytoin make its dosage regulation both difficult and important. A combination of phenytoin and phenobarbital is marketed in Yugoslavia. Since a large number of epileptic patients are treated with this combination, the opportunity was taken to assess the impact of phenytoin-phenobarbital co-medication on the calculation of Michaelis-Menten pharmacokinetic parameters and the validity of phenytoin-level prediction based on these data. Different pharmacokinetic techniques based on Michaelis-Menten principles have been reported as a means of facilitating the attainment of optimal phenytoin dosage. Some steady-state serum phenobarbital concentrations measured at different multiple doses of phenytoin but at the same multiple phenobarbital doses differed statistically significantly.
