An analysis of the Michaelis-Menten pharmacokinetics of phenytoin in epileptic Indonesian adults

Abstract

Background: Phenytoin metabolism has been shown to vary in different ethnic groups. Therefore, the authors studied phenytoin pharmacokinetics in Indonesian adult patients with epilepsy. Objective: The purpose of this study was to determine and analyse the pharmacokinetic parameters of Michaelis Menten Vmax (maximum velocity) and Km (the Michaelis constant) of phenytoin in adult epileptic patients. Method: Twelve adult epileptic patients were chosen on the basis that they had two reliable steady-state phenytoin serum levels at two different daily doses and they required an additional adjustment of phenytoin dosage monotherapy. Result: The Vmax and Km values for adult epileptic patients respectively, ranged from 3.78 to 9.65 mg/kg/day and from 0.71 to 5.58 mg/L and there was no correlation with age and weight (p > 0.05). The Vmax and Km values have shown individual variability. Conclusion: The optimal adjustment of phenytoin dose individually in adult epileptic patients based on Vmax and Km parameters needs to be done to get the desired steady-state level according to the clinical response.

Pharmacokinetic profile of phenytoin in dried blood spot with high-performance liquid chromatography—photodiode array

“…The problems encountered in phenytoin therapy can be attributed to the characteristics of the drug. Phenytoin has great interindividual pharmacological variability and a narrow therapeutic index ( Sumarno et al, 2023 ). In the distribution phase, more than 90% of phenytoin is bound to protein and does not produce a pharmacological response ( Alexander et al, 2018 ).…”

“…Small changes in plasma protein-bound phenytoin concentrations can significantly affect plasma free phenytoin concentrations, for example, due to the presence of other drugs that inhibit protein binding of phenytoin in plasma ( Alexander et al, 2018 ). In addition, phenytoin also follows nonlinear pharmacokinetics ( Sumarno et al, 2023 ). If the metabolic processes of phenytoin are saturated, small dose increases can produce large increases in plasma phenytoin concentrations and trigger toxic effects.…”