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.
Highlights
Levetiracetam, a second-generation antiepileptic drug (AED) with a unique mechanism of action, is approved by both the U.S Food and Drug Administration and the European Medicines Agency (EMA) as an add-on therapy for the treatment of partial seizures, myoclonic seizures, and primary generalized tonic-clonic seizures
Fourteen critically ill patients were enrolled in the study and all of them received intravenous (IV) levetiracetam (Keppra®) either for prophylaxis or treatment of epilepsy
The aim of this study was to investigate the pharmacokinetics of levetiracetam in critically ill intensive care adult patients and to identify possible pathophysiological factors affecting the kinetics of levetiracetam and, clinical outcome
Summary
Levetiracetam, a second-generation antiepileptic drug (AED) with a unique mechanism of action, is approved by both the U.S Food and Drug Administration and the European Medicines Agency (EMA) as an add-on therapy for the treatment of partial seizures, myoclonic seizures, and primary generalized tonic-clonic seizures. The pharmacokinetic and pharmacodynamic properties of this antiepileptic drug make it an advantageous option in the care of patients in the ICU. There is rapid and nearly complete absorption (95%) with dose-proportional pharmacokinetics, low protein binding (10%), and low within-subject variability. It is excreted primarily renally by glomerular filtration with partial tubular reabsorption and has a plasma elimination half-life of approximately 6–8 h in adults. There are no known clinically significant drug interactions, and it is not associated with the common hemodynamic or cardiovascular side effects of other AEDs [8,10,11,12]
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