title: Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.
abstract: The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.
authors.affiliation: UCB Pharma, Braine-L'Alleud, Belgium. Nathalie.Toublanc@ucb.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Toublanc
authors.affiliation: UCB Pharma, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Okagaki
authors.affiliation: Hammersmith Medicines Research, London, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Boyce
authors.affiliation: UCB Pharma, Tokyo, Japan.
authors.forename: Robert
authors.initials: R
authors.lastname: Chan
authors.affiliation: Medical Co. LTA Sumida Hospital, Tokyo, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Mugitani
authors.affiliation: UCB Pharma, Braine-L'Alleud, Belgium.
authors.forename: Shikiko
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: UCB Pharma, Tokyo, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: UCB Pharma, Tokyo, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: UCB Pharma, Braine-L'Alleud, Belgium.
authors.forename: Jens-Otto
authors.initials: JO
authors.lastname: Andreas
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D044466:Asian People; D018592:Cross-Over Studies; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D044465:White People; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam
keywords: Caucasian; E-Keppra; Intravenous; Japanese; Levetiracetam; Pharmacokinetics