title: Evaluation of the pharmacokinetics and safety of single and multiple ceftaroline fosamil infusions in healthy Chinese and Western subjects.
abstract: OBJECTIVE
  Two phase I studies in healthy Chinese (NCT01458743) and Western (NCT01612507) subjects evaluated the pharmacokinetics (PK) and safety of single and multiple ceftaroline fosamil 600 mg infusions administered every 8 or 12 hours (q8h or q12h).
  
  
  METHODS
  Each study enrolled subjects sequentially into 1 of 2 cohorts (cohort 1: 60-minute infusions; cohort 2: 120-minute infusions). All subjects in the Chinese (n = 26) study received open label ceftaroline fosamil; in the Western study, subjects (n = 41) in each cohort were randomized 3 : 1 to ceftaroline fosamil or placebo infusions. Single infusions were administered on days 1 and 8. On days 2 - 7 (3 - 7 for Chinese study, cohort 1) subjects received q12h or q8h infusions. Plasma and urine were collected on days 1 and 8 for PK analysis.
  
  
  RESULTS
  Ceftaroline PK was linear and time-independent following single and multiple doses of ceftaroline fosamil. The magnitude and timing of peak plasma concentrations of ceftaroline (active metabolite), ceftaroline fosamil (prodrug), and ceftaroline M-1 (inactive metabolite) varied according to the ceftaroline fosamil dosing schedule (q12h or q8h) and infusion duration (60 minutes or 120 minutes), but overall plasma ceftaroline exposures within the respective dosing intervals were broadly similar across cohorts. The most frequent adverse events were rash/drug eruption, most of which were of mild-moderate intensity and considered related to treatment.
  
  
  CONCLUSIONS
  Ceftaroline PK was broadly similar in healthy Chinese and Western subjects receiving equivalent dose regimens. The tolerability profile of ceftaroline fosamil in Chinese and Western subjects was consistent with previous clinical trials.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Maria
authors.initials: M
authors.lastname: Sunzel
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.forename: Timi
authors.initials: T
authors.lastname: Edeki
authors.forename: David
authors.initials: D
authors.lastname: Wilson
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D001741:Black or African American; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D044466:Asian People; D001711:Biotransformation; D002511:Cephalosporins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002681:China; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D018570:Risk Assessment; D019366:Western World; D044465:White People; D055815:Young Adult; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097583:Ceftaroline