title: Comparison of the safety, tolerability, and pharmacokinetics of fidaxomicin in healthy Japanese and caucasian subjects.
abstract: OBJECTIVE
  Fidaxomicin treatment of Clostridium difficile infection is known to produce minimal systemic exposure, as the antibacterial (antibiotic) remains primarily in the gut. In this randomized, double-blind, placebo-controlled study, the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of fidaxomicin were evaluated in healthy Japanese and Caucasian subjects.
  
  
  METHODS
  Thirty-six healthy subjects were randomly assigned in a 3:1 ratio to receive either fidaxomicin or placebo. Cohort 1 (100 mg) and Cohort 2 (200 mg) comprised 12 Japanese subjects each and Cohort 3 (200 mg) comprised 12 Caucasian subjects. Subjects received a single dose of the study drug on Day 1 and received multiple doses for 10 days after a wash-out period.
  
  
  RESULTS
  After multiple 200 mg dosing of fidaxomicin, both mean maximum plasma concentrations (C max) in Japanese (8.7 ± 5.3 ng/mL) and Caucasian (7.0 ± 3.7 ng/mL) subjects and the area under the concentration-time curve (AUC) were higher in Japanese subjects (58.5 ± 36.7 ng·h/mL) than in Caucasian subjects (37.6 ± 15.7 ng·h/mL), although variation in both groups was large. The mean fecal concentrations of fidaxomicin in Japanese and Caucasian subjects were 2669 and 2181 μg/g, respectively. The possibly study drug-related adverse events were diarrhea (n = 1), feeling hot (n = 1), and hypersomnia (n = 2), which were mild in severity.
  
  
  CONCLUSIONS
  In both Japanese and Caucasian subjects, fidaxomicin demonstrated similarly minimal systemic absorption, and was mainly excreted in feces. Fidaxomicin was safe and well-tolerated in all subjects.
authors.affiliation: Astellas Pharma Inc., 2-5-1 Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8411, Japan, hiroyuki.oshima@astellas.com.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oshima
authors.forename: Takao
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Lauren
authors.initials: L
authors.lastname: Benner
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Ingrid
authors.initials: I
authors.lastname: Michon
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wojtkowski
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kaibara
authors.forename: Salim
authors.initials: S
authors.lastname: Mujais
mesh_terms: D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D044466:Asian People; D004311:Double-Blind Method; D000077732:Fidaxomicin; D006801:Humans; D008297:Male; D008875:Middle Aged; D044465:White People; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077732:Fidaxomicin