title: Safety, tolerability and pharmacokinetics of AFN-1252 administered as immediate release tablets in healthy subjects.
abstract: OBJECTIVE
  AFN-1252 is a novel inhibitor of FabI, an essential enzyme in Staphylococcus spp. This study was undertaken to assess the safety, tolerability and pharmacokinetic properties of AFN-1252, following oral administration in an ascending dose trial.
  
  
  METHODS
  This was a double-blind, randomized, placebo-controlled, two-part study. In Part I, single doses (QD) of 100, 200, 300, or 400 mg AFN-1252 were administered. In Part II, subjects received 200, 400, 600, or 800 mg (total daily dose) where 100, 200 and 400-mg doses were given twice in one day.
  
  
  RESULTS
  AFN-1252 was well-absorbed with Cmax at 3-4 h when given once per day and 2.5-9 h when dosed twice in a single dosing day. T½ ranged from 8 to 11 h. Total and peak exposures of AFN-1252 increased nonlinearly. Adverse events were primarily mild and resolved promptly.
  
  
  CONCLUSIONS
  Oral doses of AFN-1252 were safe and well tolerated. AFN-1252 has the potential for once or twice-a-day dosing for treatment of staphylococcal infections.
authors.affiliation: Nobelex Biotech, MaRS Centre, South Tower, 101 College Street, Suite 300, Toronto, ON M5G 1L7, Canada.
authors.forename: Barry
authors.initials: B
authors.lastname: Hafkin
authors.affiliation: Nobelex Biotech, MaRS Centre, South Tower, 101 College Street, Suite 300, Toronto, ON M5G 1L7, Canada.
authors.forename: Nachum
authors.initials: N
authors.lastname: Kaplan
authors.affiliation: PPD, Inc., 7551 Metro Center Drive, Suite 200, Austin, TX 78744, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Hunt
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011753:Pyrones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013607:Tablets / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: C521531:API 1252; D000900:Anti-Bacterial Agents; D001572:Benzofurans; D010919:Placebos; D011753:Pyrones; D013607:Tablets
keywords: AFN–1252; FabI inhibitor; Phase I; Staphylococcus aureus; immediate release; pharmacokinetics; safety