title: Levetiracetam pharmacokinetics in Japanese subjects with renal impairment.
abstract: OBJECTIVE
  The anti-epileptic drug levetiracetam is excreted renally. The objective of this trial was to evaluate the pharmacokinetics of levetiracetam in Japanese patients with renal impairment including end-stage renal disease (ESRD) to confirm that existing dosing instructions-based on data from European patients-are appropriate in a Japanese population.
  
  
  METHODS
  This was a nonrandomised, open-label trial. Six participants were allocated to each of five groups (normal renal function, mild, moderate and severe renal impairment and ESRD); 30 participants in total. Participants received a single dose of levetiracetam 500 mg (normal or mild), 250 mg (moderate or severe), or 500 mg followed by 250 mg post-haemodialysis (ESRD). Blood and urine samples were obtained serially for levetiracetam and metabolite determinations. Noncompartmental pharmacokinetic parameters were calculated and steady-state profiles were simulated using the superposition method.
  
  
  RESULTS
  In this trial, levetiracetam total clearance decreased proportionally with creatinine clearance: 52, 31, 25, 20 and 11 mL/min/1.73 m(2) in healthy controls and in patients with mild, moderate, severe renal impairment, and ESRD, respectively. Simulated levetiracetam plasma profiles using the recommended dose adjustments were within the range for normal renal function. Overall, results from this trial were consistent with historical European data.
  
  
  CONCLUSIONS
  These findings confirm that the dosing instructions are appropriate for Japanese patients with renal impairment including ESRD.
authors.affiliation: UCB Pharma, Shinjuku Grand Tower, 8-17-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan, Junichi.Yamamoto@ucb.com.
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Nathalie
authors.initials: N
authors.lastname: Toublanc
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Armel
authors.initials: A
authors.lastname: Stockis
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007564:Japan; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D051437:Renal Insufficiency / Q000097:blood* / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000077287:Levetiracetam; D010889:Piracetam