JAC Advance Access originally published online on February 25, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Antimicrobial Chemotherapy (2003) 51, 939-945
© 2003 The British Society for Antimicrobial Chemotherapy
Comparative distribution of azithromycin in lung tissue of patients given oral daily doses of 500 and 1000 mg
1 Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, 55 Via Roma; 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
Received 3 August 2002; returned 27 October 2002; revised 8 December 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
* Corresponding author. Tel: +39-050-830148; Fax: +39-050-562020; E-mail: r.danesi{at}med.unipi.it
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Lucchi, B. Damle, A. Fang, P. J. de Caprariis, A. Mussi, S. P. Sanchez, G. Pasqualetti, and M. Del Tacca Pharmacokinetics of azithromycin in serum, bronchial washings, alveolar macrophages and lung tissue following a single oral dose of extended or immediate release formulations of azithromycin J. Antimicrob. Chemother., April 1, 2008; 61(4): 884 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sevillano, L. Alou, L. Aguilar, O. Echevarria, M.-J. Gimenez, and J. Prieto Azithromycin iv pharmacodynamic parameters predicting Streptococcus pneumoniae killing in epithelial lining fluid versus serum: an in vitro pharmacodynamic simulation J. Antimicrob. Chemother., June 1, 2006; 57(6): 1128 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Carfartan, P. Gerardin, D. Turck, and M.-O. Husson Effect of subinhibitory concentrations of azithromycin on adherence of Pseudomonas aeruginosa to bronchial mucins collected from cystic fibrosis patients J. Antimicrob. Chemother., April 1, 2004; 53(4): 686 - 688. [Full Text] [PDF]
|
|