The Pharmacokinetics of Levetiracetam in Critically Ill Adult Patients: An Intensive Care Unit Clinical Study

Abstract

The aim of this study was to investigate levetiracetam pharmacokinetics in critically ill adult intensive care patients and to identify pathophysiological factors affecting its kinetics. Fourteen critically ill patients in an intensive care unit were enrolled in the study and received intravenous levetiracetam. Blood samples were collected at specific time points to determine the levetiracetam pharmacokinetics. Patient characteristics such as renal function, demographics, disease severity, organ dysfunction, and biochemical laboratory tests were evaluated for their influence on the kinetics of levetiracetam. Estimated glomerular filtration rate (eGFR) had a statistically significant (p = 0.001) effect on levetiracetam clearance. None of the other patient characteristics had a statistically significant effect on the pharmacokinetics. Simulations of dosing regimens revealed that even typically administered doses of levetiracetam may result in significantly increased concentrations and risk of drug toxicity in patients with impaired renal function. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score differed significantly among the three groups with different epileptic activity (p = 0.034). The same groups also differed in terms of renal function (p = 0.031). Renal dysfunction should be considered when designing levetiracetam dosage. Patients with a low APACHE II score had the lowest risk of experiencing epileptic seizures.

Keywords

• levetiracetam
• critically ill patients
• population pharmacokinetic modeling
• simulated dosage schemes
• intensive care unit