title: Results of phase II pharmacokinetic study of levetiracetam for prevention of post-traumatic epilepsy.
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 T(max) was 2.2h, C(max) was 60.2μg/ml and AUC was 403.7μg/h/ml. T(max) 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). C(max) 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.
authors: Department of Neurology, MedStar Research Institute, Washington, D.C. 20010, USA. kleinp@epilepsydc.com
authors: Pavel
authors: P
authors: Klein
authors: Daniel
authors: D
authors: Herr
authors: Phillip L
authors: PL
authors: Pearl
authors: JoAnne
authors: J
authors: Natale
authors: Zachary
authors: Z
authors: Levine
authors: Claude
authors: C
authors: Nogay
authors: Fabian
authors: F
authors: Sandoval
authors: Stacey
authors: S
authors: Trzcinsky
authors: Shireen M
authors: SM
authors: Atabaki
authors: Tammy
authors: T
authors: Tsuchida
authors: John
authors: J
authors: van den Anker
authors: Steven J
authors: SJ
authors: Soldin
authors: Jianping
authors: J
authors: He
authors: Robert
authors: R
authors: McCarter
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D001930:Brain Injuries / Q000150:complications; D002648:Child; D003404:Creatinine / Q000097:blood; D004827:Epilepsy / Q000097:blood / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D015600:Glasgow Coma Scale; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D003404:Creatinine; D011494:Protein Kinases; D010889:Piracetam