title: Steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients.
abstract: OBJECTIVE
  To characterize the steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients requiring seizure prophylaxis after a neurologic injury and to determine which dosing regimens achieve serum concentrations within the recommended therapeutic range of 6-20 μg/ml. DESIGN. Prospective, open-label, steady-state pharmacokinetic study.
  
  
  METHODS
  Neurocritical care unit in a tertiary care medical center. PATIENTS. Twelve adults (five men, seven women) admitted to the neurocritical care unit who required prophylactic anticonvulsant therapy after subarachnoid hemorrhage, subdural hematoma, or traumatic brain injury.
  
  
  METHODS
  Patients received an intravenous infusion of levetiracetam 500 mg over 15 minutes every 12 hours.
  
  
  RESULTS
  Serial blood samples were collected from all patients after a minimum of four doses of therapy. Serum levetiracetam concentrations were determined by ultraperformance liquid chromatography with tandem mass spectrometry detection, and pharmacokinetic data were analyzed by compartmental and noncompartmental methods. Monte Carlo simulations were performed for multiple levetiracetam dosing regimens to determine the probability of achieving a target trough concentration of 6 μg/ml or greater, 20 μg/ml or greater, and 6-20 μg/ml. The mean ± SD levetiracetam maximum serum concentration was 28.0 ± 8.0 μg/ml, minimum serum concentration 3.1 ± 1.8 μg/ml, half-life 5.2 ± 1.2 hours, systemic clearance 5.6 ± 1.8 L/hour, and volume of distribution at steady state 36.8 ± 6.3 L. Increasing the doses of levetiracetam increased the probability of achieving a target trough concentration of 6 μg/ml or greater but also increased the probability of achieving trough concentrations greater than 20 μg/ml. Levetiracetam doses of 1000 mg every 8 hours and 1500-2000 mg every 12 hours provided the highest probability of achieving a target trough concentration between 6 and 20 μg/ml.
  
  
  CONCLUSIONS
  Compared with previously published results in healthy volunteers and adults in status epilepticus, levetiracetam systemic clearance was faster and the terminal elimination half-life was shorter in neurocritical care patients. Higher doses or more frequent dosing may be needed to achieve target trough concentrations of 6-20 μg/ml.
authors.affiliation: Department of Pharmacy, Indiana University Health, Methodist Hospital, Indianapolis, Indiana 46202, USA. dspence2@iuhealth.org
authors.forename: Dustin D
authors.initials: DD
authors.lastname: Spencer
authors.forename: Judith
authors.initials: J
authors.lastname: Jacobi
authors.forename: Joetta M
authors.initials: JM
authors.lastname: Juenke
authors.forename: James D
authors.initials: JD
authors.lastname: Fleck
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kays
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001930:Brain Injuries / Q000097:blood / Q000150:complications / Q000628:therapy; D003422:Critical Care / Q000379:methods*; D005260:Female; D006408:Hematoma, Subdural / Q000097:blood / Q000150:complications / Q000628:therapy; D006801:Humans; D007262:Infusions, Intravenous; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011446:Prospective Studies; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000150:complications / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam