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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. 2008 Apr; 61(4):884-91.JA

Abstract

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.

Authors+Show Affiliations

Division of Thoracic Surgery, Cardiothoracic Department, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18252692

Citation

Lucchi, M, et al. "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." The Journal of Antimicrobial Chemotherapy, vol. 61, no. 4, 2008, pp. 884-91.
Lucchi M, Damle B, Fang A, et al. 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. 2008;61(4):884-91.
Lucchi, M., Damle, B., Fang, A., de Caprariis, P. J., Mussi, A., Sanchez, S. P., Pasqualetti, G., & Del Tacca, M. (2008). 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. The Journal of Antimicrobial Chemotherapy, 61(4), 884-91. https://doi.org/10.1093/jac/dkn032
Lucchi M, et al. 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. 2008;61(4):884-91. PubMed PMID: 18252692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Lucchi,M, AU - Damle,B, AU - Fang,A, AU - de Caprariis,P J, AU - Mussi,A, AU - Sanchez,S P, AU - Pasqualetti,G, AU - Del Tacca,M, Y1 - 2008/02/04/ PY - 2008/2/7/pubmed PY - 2008/4/16/medline PY - 2008/2/7/entrez SP - 884 EP - 91 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 61 IS - 4 N2 - 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. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/18252692/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_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkn032 DB - PRIME DP - Unbound Medicine ER -