title: Comparative distribution of azithromycin in lung tissue of patients given oral daily doses of 500 and 1000 mg.
abstract: OBJECTIVE
  The administration of antibacterial agents should be optimized on the basis of their distribution to enhance drug exposure and obtain bacterial eradication. This study examines the pharmacokinetics of azithromycin in plasma, lung tissue and bronchial washing in patients after oral administration of 500 mg versus 1000 mg once daily for 3 days.
  
  
  METHODS
  Samples of plasma, lung tissue and bronchial washing were obtained from a cohort of 48 patients during open-chest surgery for lung resection up to 204 h after the last drug dose, and assayed for antibiotic concentrations.
  
  
  RESULTS
  Azithromycin was widely distributed within the lower respiratory tract and sustained levels of the drug were detectable at the last sampling time in lung tissue. Doubling the dose of the antibiotic resulted in a proportional increase in lung area under the curve (AUC, 1245.4 versus 2514.2 h x mg/kg) and peak tissue concentration (Cmax, 8.93 +/- 2.05 versus 18.6 +/- 2.20 mg/kg). The pharmacodynamic parameter AUC/MIC for susceptible and intermediate strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L, respectively) increased after administration of the 1000 mg schedule compared with 500 mg (AUC/MIC0.5 2414 versus 1144 and AUC/MIC2 2112 versus 814.1 h x mg/kg, respectively) in pulmonary tissue.
  
  
  CONCLUSIONS
  Lung exposure to azithromycin is increased proportionally by doubling the dose, which results in a predictable pharmacokinetic behaviour of the drug in the lower respiratory tract.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, 55 Via Roma, Italy. r.danesi@med.unipi.it
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Antonella
authors.initials: A
authors.lastname: Lupetti
authors.forename: Cecilia
authors.initials: C
authors.lastname: Barbara
authors.forename: Emilia
authors.initials: E
authors.lastname: Ghelardi
authors.forename: Antonio
authors.initials: A
authors.lastname: Chella
authors.forename: Tecla
authors.initials: T
authors.lastname: Malizia
authors.forename: Sonia
authors.initials: S
authors.lastname: Senesi
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Angeletti
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
authors.forename: Mario
authors.initials: M
authors.lastname: Campa
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001681:Biological Assay; D001980:Bronchi / Q000378:metabolism; D015331:Cohort Studies; D006207:Half-Life; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000601:surgery; D016982:Micrococcus luteus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin