PHARMACOKINETICS OF AZITHROMYCIN IN LUNG TISSUE, BRONCHIAL WASHING, AND PLASMA IN PATIENTS GIVEN MULTIPLE ORAL DOSES OF 500 AND 1000 MG DAILY
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INTRODUCTION
Azithromycin is an azalide antibiotic that contains a nitrogen atom in the macrolide aglycone ring. The drug is active in vitro against Streptococcus pneumoniae, group A streptococci, Streptococcus agalactiae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis and intracellular organisms such as Chlamydia, Mycoplasma, and Legionella species [1]. Azithromycin retains the Gram-positive activity of erythromycin as the result of a common mechanism of action but provides
Study design and subjects
This open-label, unblinded, randomized trial was approved by the Ethics Committee of Pisa University Hospital. Patients were advised of the aim and investigational nature of this study and they were considered to be eligible after providing a written informed consent. Patients of either sex, 35–70 years of age, affected by noninfectious lung diseases, requiring open-chest surgery with lung resection, qualified to be included if nonsmokers or with a history of cigarette smoking of less than 5
RESULTS
Two groups of 28 patients each were enrolled in the study; 18 males and 10 females (age range 36–70 years, median age 64 years) were given azithromycin at the 500 mg dose level, while 19 males and 9 females (age range 35–69 years, median age 61 years) received azithromycin at the 1000 mg dose level. No serious adverse events were reported; mild gastrointestinal discomfort and loose stools, not requiring discontinuation of azithromycin administration, were noticed by few patients, without
DISCUSSION
The selection of an antimicrobial agent for the treatment of an infection is usually based on information given by the MICs and the time versus concentration profile of the drugs in plasma (i.e. pharmacokinetic data). Thus, individual drug doses and dosing intervals are tailored to achieve concentrations in serum that are above the MIC throughout the dosing interval. The MIC, however, is only one of the factors that need to be considered for the selection of an appropriate antimicrobial agent
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2014, Pharmacology and TherapeuticsCitation Excerpt :The distribution of azithromycin into inflamed tissues and compartments has been extensively investigated. In bronchial washings and lung tissue biopsy specimens (Di Paolo et al., 2002), in lungs, in sinus mucosal tissue (Ehnhage et al., 2008; Fang et al., 2009), in middle ear fluids in children with otitis media (Pukander & Rautianen, 1996; Scaglione et al., 1999), in the aqueous humor and in conjunctival biopsy specimens (Tabbara et al., 1998), in tissues lining periodontal pockets (Gomi et al., 2007), and in inflammatory skin blisters (Ballow et al., 1998), azithromycin concentrations were always higher than those in plasma. This tissue accumulation offsets the sub-optimal absorption of the drug.
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