What Are the Predictors for Achieving Therapeutic Levetiracetam Serum Concentrations in Adult Neurological Patients?

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/ss was 11.5 (7.0-16.5) mg/L. The coefficient of variation of Cmin/ss and dose-normalized Cmin/ss were 69.4% and 64.2%, respectively. A weak correlation was observed between levetiracetam Cmin/ss and 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/ss attainment. 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.