Levetiracetam Pharmacokinetics During Continuous Venovenous Hemofiltration and Acute Liver Dysfunction

Abstract

Levetiracetam pharmacokinetics observed in this case approximated those seen in a normal healthy patient and a regimen of 1000 mg twice daily achieved serum trough concentrations at the lower limit of the target range. This case indicates that in a patient with acute liver dysfunction on CVVH, 1000 mg twice daily may be considered as an empiric levetiracetam regimen.

Levetiracetam Pharmacokinetics in a Patient with Intracranial Hemorrhage Undergoing Continuous Veno-Venous Hemofiltration

“…Two of these case reports used a single steady-state trough concentration for each of their pharmacokinetic evaluations, introducing possible error due to the use of population estimates [16,18]. Comorbidities such as hepatic failure and the need for extracorporeal membrane oxygenation also complicate the evaluation of the role CRRT plays in levetiracetam [17,18].…”

“…Two of these case reports used a single steady-state trough concentration for each of their pharmacokinetic evaluations, introducing possible error due to the use of population estimates [16,18]. Comorbidities such as hepatic failure and the need for extracorporeal membrane oxygenation also complicate the evaluation of the role CRRT plays in levetiracetam [17,18]. The present report used an extensive sampling strategy including effluent sampling to isolate the role CVVH in the elimination of levetiracetam and to establish a sieving coefficient for levetiracetam, but is limited in that the sample was a single patient, and by pharmaco-kinetic differences within the neurocritically ill. Globally, levetiracetam therapeutic drug monitoring is limited as there is not an established relationship between plasma concentrations and clinical efficacy of levetiracetam.…”

“…These reports had complicating factors such as inclusion of patients with acute liver dysfunction, limited sampling strategies, concomitant use of extracorporeal membrane oxygenation, and a lack of effluent concentrations to determine clearance associated with CRRT; these factors may limit applicability to other critically ill patients requiring CRRT [16–18]. We report the case of a patient with an intraparenchymal hemorrhage on CRRT who received seizure prophylaxis therapy with intravenous levetiracetam.…”

Extracorporeal Clearance of Levetiracetam During Continuous Venovenous Hemofiltration in a Critically Ill Patient and New Dosing Recommendation

“…Our new CVVH dosage regimen based on the calculated MDMF of 3.6 might prevent underdosing. In addition to the sieving coefficient of 0.89, a low‐molecular‐weight (170.2 DaD), low‐protein bound fraction (10%), and low volume of levetiracetam distribution (< 0.7 L/kg) could all account for the significant CVVH clearance . Based on our pharmacokinetic simulations, we recommend a levetiracetam dose adjustment of 2000 mg/24 h using continuous intravenous dosing in patients receiving CVVH (Figure ).…”

“…Levetiracetam is a widely used antiepileptic drug; however, robust dosing recommendations for adult patients receiving continuous venovenous hemofiltration (CVVH) are lacking . The present intermittent dosage recommendation of 1000 mg every 12 hours is based on 3 case reports . Although useful, data on renal clearance, clearance by CVVH (CL CVVH ) and the maintenance dose multiplication factor (MDMF) are not available.…”