title: Pharmacokinetics of ethambutol in children and adults with tuberculosis.
abstract: METHODS
  Five hospitals in the United States.
  
  
  OBJECTIVE
  To describe ethambutol pharmacokinetics in children and adults with active tuberculosis (TB).
  
  
  METHODS
  Prospective, open-labeled study in 56 adults and 14 children with active tuberculosis who received ethambutol as part of their multidrug TB regimens.
  
  
  RESULTS
  Most serum samples were collected up to 10 h post dose and assayed using a validated gas chromatography assay with mass selective detection (GC/MS). Concentration data were analyzed using non-compartmental and population pharmacokinetic methods. Drug exposure increased with dose, but less than proportionally at doses >3000 mg. Lower than expected maximum serum concentrations (Cmax <2 microg/ml) were common in adults. Very low Cmax (<1 microg/ml) were common in children, as was delayed absorption (time to Cmax >3 h). Many Cmax were at or below typical TB minimal inhibitory concentrations. Cmax values for HIV-positive patients were 20% lower than HIV-negative patients with daily doses, but were similar with larger twice-weekly doses.
  
  
  CONCLUSIONS
  Adult TB patients often had lower than expected ethambutol serum concentrations, and most pediatric TB patients had very low ethambutol serum concentrations. Higher doses and therapeutic drug monitoring may be indicated for many of these patients.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.forename: W J
authors.initials: WJ
authors.lastname: Burman
authors.forename: J R
authors.initials: JR
authors.lastname: Starke
authors.forename: J J
authors.initials: JJ
authors.lastname: Stambaugh
authors.forename: P
authors.initials: P
authors.lastname: Steiner
authors.forename: A E
authors.initials: AE
authors.lastname: Bulpitt
authors.forename: D
authors.initials: D
authors.lastname: Ashkin
authors.forename: B
authors.initials: B
authors.lastname: Auclair
authors.forename: S E
authors.initials: SE
authors.lastname: Berning
authors.forename: R W
authors.initials: RW
authors.lastname: Jelliffe
authors.forename: G S
authors.initials: GS
authors.lastname: Jaresko
authors.forename: C A
authors.initials: CA
authors.lastname: Peloquin
mesh_terms: D000042:Absorption; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004977:Ethambutol / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000378:metabolism*; D014481:United States; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol