What are the predictors for achieving therapeutic levetiracetam serum concentrations in adult neurological patients?

Abstract

Background:Emerging studies suggest that levetiracetam pharmacokinetics can be difficult to predict in certain special patient populations, including the elderly, critically ill patients, and pregnant women.Objective:To determine clinical characteristics that predict the attainment of target serum concentrations in a heterogeneous group of patients prescribed levetiracetam.Methods:A retrospective observational study was conducted in adult neurological patients prescribed levetiracetam for the treatment or prophylaxis of seizures. Serum samples were collected after steady-state was reached, with a trough/steady-state serum concentration between 6 and 20 mg/L considered therapeutic. Logistic regression was used to identify significant predictors associated with the attainment of therapeutic concentrations.Results:One-hundred thirty patients (63 male) were included. The median (interquartile ranges) serum trough/steady-state concentration (Cmin/ss) was 16.2 (9.8-26.1) mg/L. The dose-normalized median (interquartile range) Cmin/sswas 11.5 (7.0-16.5) mg/L. The coefficient of variation of Cmin/ssand dose-normalized Cmin/sswere 69.4% and 64.2%, respectively. A weak correlation was observed between levetiracetam Cmin/ssand patient age (r = 0.21; P = 0.020), creatinine clearance (r = -0.26; P = 0.004), and daily dose (r = 0.42; P < 0.001). Logistic regression analysis identified age and daily levetiracetam dose as significant factors predicting target Cmin/ssattainment. The influence of concomitant antiepileptic therapy was not determined.Conclusions:Age and daily dose were the most significant predictors of levetiracetam target-concentration attainment and should be considered in further investigations to develop a dosing algorithm for optimal levetiracetam therapy.