title: Open-label, nonrandomized study of the effects of gatifloxacin on the pharmacokinetics of midazolam in healthy male volunteers.
abstract: OBJECTIVE
  To confirm findings from an in vitro study that showed gatifloxacin did not substantially inhibit cytochrome P450 (CYP) 3A4 model substrate metabolism.
  
  
  METHODS
  Open-label, nonrandomized trial.
  
  
  METHODS
  Clinical pharmacology unit.
  
  
  METHODS
  Fourteen healthy adult men.
  
  
  METHODS
  Using midazolam probe methodology, the clearance of midazolam in the presence of multiple-dose gatifloxacin was evaluated.
  
  
  RESULTS
  Typical steady-state concentrations of gatifloxacin 400 mg once/day had no effect on midazolam clearance, and gatifloxacin pharmacokinetics were unaffected by midazolam. All doses of both agents were well tolerated.
  
  
  CONCLUSIONS
  Data from this in vivo trial support in vitro experience with gatifloxacin and suggest that interactions are unlikely between gatifloxacin and drugs that are metabolized by CYP3A.
authors.affiliation: Department of Clinical Pharmacology, Bristrol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Grasela
authors.forename: F P
authors.initials: FP
authors.lastname: LaCreta
authors.forename: G D
authors.initials: GD
authors.lastname: Kollia
authors.forename: D M
authors.initials: DM
authors.lastname: Randall
authors.forename: H D
authors.initials: HD
authors.lastname: Uderman
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D006801:Humans; D008297:Male; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012016:Reference Values
chemical_list: D000890:Anti-Infective Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D024841:Fluoroquinolones; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D000077734:Gatifloxacin; D008874:Midazolam