title: The pharmacokinetic and safety profiles of zanamivir after single and repeat intravenous administration in healthy Japanese males.
abstract: OBJECTIVE
  Neuraminidase inhibitors are important options for the treatment of infection by the influenza virus. For the treatment of severe influenza, parenteral administration of a neuraminidase inhibitor may be desirable. This study was conducted to evaluate the pharmacokinetic and safety profiles of intravenous zanamivir, an influenza viral neuraminidase inhibitor, in Japanese subjects to further characterize these profiles particularly following relatively high-doses when compared with inhalation doses and to provide reassurance that there are no marked differences with profiles reported for other ethnically different populations.
  
  
  METHODS
  Single doses of 100, 300, 600 mg zanamivir were administered to healthy Japanese men in a randomized, double-blind, ascending dose, placebo-controlled, incomplete three-period cross-over study. In period 3, subjects were given 600 mg of zanamivir on day 1, followed by a 60 h washout period and then a 5-day course of 600 mg zanamivir twice daily. Each subjects received two of three active dosages of zanamivir from 100, 300 and 600 mg, and placebo.
  
  
  RESULTS
  Adverse events reported in the study were all mild in intensity and resolved without any treatment. The mean AUC0-∞ values after single intravenous administration of 100, 300 and 600 mg were 16768, 53462 and 100400 ng·h/mL, respectively, demonstrating dose proportionality. No accumulation or time variance was observed after 5 days of twice-daily administration of 600 mg zanamivir. Urinary concentrations of zanamivir after single doses ranging from 100 to 600 mg indicated that over 94% of the zanamivir administered was excreted in urine within 24 h.
  
  
  CONCLUSIONS
  Single and 5-day BID repeat dosing of 600 mg were safely administered in Japanese healthy subjects. The pharmacokinetic profile of zanamivir after intravenous administration was consistent with previously reported findings in non-Japanese subjects.
authors.affiliation: Clinical Pharmacology Department, Medicines Development, Development & Medical Affairs Division, GlaxoSmithKline K.K, Tokyo, Japan. yuri.2.shida@gsk.com
authors.forename: Y
authors.initials: Y
authors.lastname: Shida
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: S
authors.initials: S
authors.lastname: Nohda
authors.forename: T
authors.initials: T
authors.lastname: Soutome
authors.forename: T
authors.initials: T
authors.lastname: Hirama
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D055815:Young Adult; D053243:Zanamivir / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009439:Neuraminidase; D053243:Zanamivir