title: Safety, tolerability and pharmacokinetics of multiple oral doses of AFN-1252 administered as immediate release (IR) tablets in healthy subjects.
abstract: BACKGROUND
  AFN-1252 is a novel inhibitor of FabI, which is essential in Staphylococcus spp. This study evaluated the safety, tolerability and pharmacokinetics of multiple oral doses of AFN-1252 immediate-release tablets.
  
  
  METHODS
  Part I evaluated AFN-1252 as a single 200 mg dose in fed versus fasted subjects. Part II evaluated 200, 300 and 400 mg doses of AFN-1252 administered once-daily for 10 days.
  
  
  RESULTS
  Pharmacokinetics indicated good absorption with a median Tmax of 2-3 hours, and a mean t1/2 of 7-10 hours, for all doses. Cmax and AUC responses were non-linear. A high-fat meal reduced AUC0-t and Cmax values by 62% and 48%, respectively, and delayed Tmax by 2.5 hours. All adverse events, including possibly drug-related headache and nausea, were mild or moderate.
  
  
  CONCLUSIONS
  Multiple ascending doses of AFN-1252 were safe and well tolerated. AFN-1252 has potential for once- or twice-daily dosing in the treatment of staphylococcal infections.
authors.affiliation: a Pharmaceutical Product Development Inc , Austin , TX , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hunt
authors.affiliation: b Affinium Pharmaceuticals, Inc.
authors.forename: Nachum
authors.initials: N
authors.lastname: Kaplan
authors.affiliation: b Affinium Pharmaceuticals, Inc.
authors.forename: Barry
authors.initials: B
authors.lastname: Hafkin
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015331:Cohort Studies; D018592:Cross-Over Studies; D005215:Fasting; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011753:Pyrones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013607:Tablets; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: C521531:API 1252; D000900:Anti-Bacterial Agents; D001572:Benzofurans; D011753:Pyrones; D013607:Tablets
keywords: AFN-1252; FabI inhibitor; Immediate–release; Multiple dose; Pharmacokinetics; Phase I; Safety; Staphylococcus aureus