Comparative distribution of azithromycin in lung tissue of patients given oral daily doses of 500 and 1000 mg.
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.
Danesi
Romano
R
Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, 55 Via Roma, Italy. r.danesi@med.unipi.it
Lupetti
Antonella
A
Barbara
Cecilia
C
Ghelardi
Emilia
E
Chella
Antonio
A
Malizia
Tecla
T
Senesi
Sonia
S
Angeletti
Carlo Alberto
CA
Del Tacca
Mario
M
Campa
Mario
M
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
D000900:Anti-Bacterial Agents; D017963:Azithromycin