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Author Topic: Farmakokinetika azitromicina u serumu, alveolarnim makrofagama ...  (Read 3524 times)

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Farmakokinetika azitromicina u serumu, alveolarnim makrofagama, plucnom tkivu datom oralno u jednoj dozi  u formulacijama sa  produzenim ili momentalnim oslobadjanjem azitromicina

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.

Lucchi M, Damle B, Fang A, de Caprariis PJ, Mussi A, Sanchez SP, Pasqualetti G, Del Tacca M.

Division of Thoracic Surgery, Cardiothoracic Department, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.

Objectives Antibacterial efficacy of azithromycin could be improved by achieving higher concentrations at the sites of infection. Azithromycin extended release (azithromycin-ER) formulation was developed to enable a higher dosage of 2 g to be administered as a single oral dose without decreasing the safety profile. The aim of this study was to compare the pharmacokinetics of azithromycin in serum, epithelial lining fluid (ELF), alveolar macrophages (AMs) and lung tissue following a single oral dose of azithromycin-ER or azithromycin immediate release (azithromycin-IR) formulation. Patients and methods A total of 64 patients, diagnosed with lung cancer, requiring open-chest surgery for lung resection, completed the study. Subjects were randomized to receive oral administration of either a single 2 g dose of azithromycin-ER (32 subjects) or a single 500 mg dose of azithromycin-IR (32 subjects). Simultaneously, subjects within each treatment group were randomized to one of eight specific nominal post-dose time points for bronchoalveolar lavage and lung tissue sampling. Results For azithromycin-IR formulation, the AUC(0-24) in serum, ELF, AMs and lung tissue was 3.1, 2.3, 1674 mg.h/L and 130 mg.h/kg, respectively. For azithromycin-ER formulation, the AUC(0-24) in serum, ELF, AMs and lung tissue were 10.0, 17.6, 7028 mg.h/L and 505 mg.h/kg, respectively. The AUC(0-24) ratio following administration of azithromycin-ER relative to azithromycin-IR was 3.2, 7.7, 4.2 and 3.9 in serum, ELF, AMs and lung tissue, respectively. Conclusions Within the first 24 h, a single 2 g azithromycin-ER dose produced dose-related increase in systemic exposure compared with a single 500 mg azithromycin-IR dose, which resulted in higher levels of azithromycin in ELF, AMs and lung tissue. Both formulations had similar safety profiles. By achieving high azithromycin exposure early in the course of treatment, without compromising tolerability, azithromycin-ER shows the potential for improved antibacterial efficacy compared with azithromycin-IR.

izvor:
http://www.peerview-institute.org/news/content.nsf/NTKPaperFrameSet?OpenForm&pp=1&id=317AC309768BE86B8525727D004E4FE2&newsid=852571020057CCF6852573E9002F30BE&locref=ntkwatch&u=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18252692


 

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