Results of phase II pharmacokinetic study of levetiracetam for prevention of post-traumatic epilepsy

Pavel Klein, Daniel Herr, Phillip L. Pearl, JoAnne E Natale, Zachary Levine, Claude Nogay, Fabian Sandoval, Stacey Trzcinsky, Shireen M. Atabaki, Tammy Tsuchida, John van den Anker, Steven J. Soldin, Jianping He, Robert McCarter

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Levetiracetam (LEV) has antiepileptogenic effects in animals and is a candidate for prevention of epilepsy after traumatic brain injury. Pharmacokinetics of LEV in TBI patients was unknown. We report pharmacokinetics of TBI subjects≥6years with high PTE risk treated with LEV 55mg/kg/day orally, nasogastrically or intravenously for 30days starting ≤8h after injury in a phase II safety and pharmacokinetic study. Forty-one subjects (26 adults and 15 children) were randomized to PK studies on treatment days 3 and 30. Thirty-six out of forty-one randomized subjects underwent PK study on treatment day 3, and 24/41 subjects underwent PK study on day 30. On day 3, mean Tmax was 2.2h, Cmax was 60.2μg/ml and AUC was 403.7μg/h/ml. Tmax was longer in the elderly than in children and non-elderly adults (5.96h vs. 1.5h and 1.8h; p=0.0001). AUC was non-significantly lower in children compared with adults and the elderly (317.4μg/h/ml vs. 461.4μg/h/ml and 450.2μg/h/ml; p=0.08). Cmax trended higher in i.v.- versus tablet- or n.g.-treated subjects (78.4μg/ml vs. 59μg/ml and 48.2μg/ml; p=0.07). AUC of n.g. and i.v. administrations was 79% and 88% of AUC of oral administration. There were no significant PK differences between days 3 and 30. Treatment of TBI patients with high PTE risk with 55mg/kg/day LEV, a dose with antiepileptogenic effect in animals, results in plasma LEV levels comparable to those in animal studies.

Original languageEnglish (US)
Pages (from-to)457-461
Number of pages5
JournalEpilepsy and Behavior
Volume24
Issue number4
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Epilepsy
  • Epilepsy prevention
  • Head injury
  • Levetiracetam
  • Pharmacokinetics
  • Post-traumatic epilepsy
  • Saliva
  • Seizures
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Behavioral Neuroscience
  • Neurology

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