Levetiracetam Pharmacokinetics During Continuous Venovenous Hemofiltration and Acute Liver Dysfunction

• Published in: Neurocritical care 2016-08, Vol.25 (1), p.141-144
• Main Authors: New, Andrea M., Nei, Scott D., Kashani, Kianoush B., Rabinstein, Alejandro A., Frazee, Erin N.
• Format: Article
• Language: English
• Subjects: Anemia; Anticonvulsants - pharmacokinetics; Blood tests; Case reports; Convulsions & seizures; Critical Care Medicine; Drug dosages; Drug interactions; Extracorporeal membrane oxygenation; Hemofiltration - methods; Humans; Intensive; Internal Medicine; Kidneys; Liver cirrhosis; Liver Failure, Acute - therapy; Male; Medical laboratories; Medicine; Medicine & Public Health; Middle Aged; Molecular weight; Neurology; Patients; Pharmacokinetics; Piracetam - analogs & derivatives; Piracetam - pharmacokinetics; Practical Pearl; Renal Insufficiency - therapy; Therapeutic drug monitoring
• ISSN: 1541-6933; 1556-0961
• DOI: 10.1007/s12028-016-0242-1

Background Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction. Methods This is a case report of a single patient. Results A 59-year-old male was admitted to the intensive care unit for acute onset multiorgan dysfunction associated with a hematologic disorder. His hospital course was complicated by persistent liver dysfunction with a model for end-stage liver disease score of 47 and renal failure which necessitated initiation of CVVH. On hospital day two, the patient developed new-onset focal seizures secondary to metabolic abnormalities that resulted in the initiation of levetiracetam 1000 mg intravenously twice daily. The peak concentration at steady state was 32.2 mcg/mL, and the trough concentration was 16.1 mcg/mL (goal 12–46 mcg/mL). The volume of distribution was 0.65 L/kg, and the elimination half-life was 11.4 h. Conclusion 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.