title: Penetration of clarithromycin into middle ear fluid of children with acute otitis media.
abstract: OBJECTIVE
  To determine the steady state plasma and middle ear fluid concentrations of clarithromycin and its metabolite, 14(R)-hydroxyclarithromycin in 32 pediatric patients with acute otitis media.
  
  
  METHODS
  After the sixth dose of a 7.5-mg/kg every-12-h regimen of clarithromycin suspension, tympanocentesis was performed at 2, 4, 8 or 12 hours postdose. Plasma and middle ear fluid samples were assayed for concentrations of clarithromycin and its 14-hydroxy metabolite.
  
  
  RESULTS
  Mean middle ear fluid concentrations ranged from 3.0 to 8.3 micrograms/g during the dosing interval for clarithromycin and from 1.5 to 3.8 micrograms/g for 14(R)-hydroxyclarithromycin. The mean middle ear fluid concentrations were consistently greater than corresponding mean plasma concentrations, which ranged from 0.7 to 3.4 micrograms/ml for clarithromycin and from 0.8 to 1.8 micrograms/ml for 14(R)-hydroxyclarithromycin. The ratios of middle ear fluid to plasma concentration appeared to increase during the dosing interval and were 8.8 and 3.8 for clarithromycin and 14(R)-hydroxyclarithromycin, respectively, 12 h after dosing.
  
  
  CONCLUSIONS
  Multiple oral doses of clarithromycin suspension produced sustained middle ear fluid concentrations of clarithromycin and 14(R)-hydroxyclarithromycin which exceed the minimum inhibitory concentrations of most otic pathogens.
authors.affiliation: Children's Medical Center of Dallas, TX 75235, USA. vangan@childmed.dallas.tx.us
authors.forename: V N
authors.initials: VN
authors.lastname: Gan
authors.forename: J M
authors.initials: JM
authors.lastname: McCarty
authors.forename: S Y
authors.initials: SY
authors.lastname: Chu
authors.forename: R
authors.initials: R
authors.lastname: Carr
mesh_terms: D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D017291:Clarithromycin / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004432:Ear, Middle / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010034:Otitis Media with Effusion / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; C056228:14-hydroxyclarithromycin; D017291:Clarithromycin