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 journalArticle

25 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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  • Cite this

    Klein, P., Herr, D., Pearl, P. L., Natale, J. E., Levine, Z., Nogay, C., Sandoval, F., Trzcinsky, S., Atabaki, S. M., Tsuchida, T., van den Anker, J., Soldin, S. J., He, J., & McCarter, R. (2012). Results of phase II pharmacokinetic study of levetiracetam for prevention of post-traumatic epilepsy. Epilepsy and Behavior, 24(4), 457-461. https://doi.org/10.1016/j.yebeh.2012.05.011