JAC Advance Access published online on February 25, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg138
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Division of Pharmacology
and Chemotherapy, Department of Oncology, Transplants and Advanced
Technologies in Medicine, 55 Via Roma
* Corresponding author. E-mail: r.danesi{at}med.unipi.it.
Received 3 August 2002
; revised 27 October 2002
; accepted 6 January 2003
Objectives: 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. Patients and 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.
Keywords: pharmacokinetics, microbiological assay, azalide, Streptococcus pneumoniae, pharmacodynamics
Comparative distribution of azithromycin in lung
tissue of patients given oral daily doses of 500 and 1000 mg
2 Section of Microbiology, Department of Experimental
Pathology,
Medical Biotechnologies, Infectious Diseases and Epidemiology, 39
Via S. Zeno
3 Division of
Thoracic Surgery,
Cardio-Thoracic Department, 2 Via Paradisa, University of Pisa,
56100 Pisa, Italy
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