Elsevier

Pharmacological Research

Volume 46, Issue 6, December 2002, Pages 545-550
Pharmacological Research

PHARMACOKINETICS OF AZITHROMYCIN IN LUNG TISSUE, BRONCHIAL WASHING, AND PLASMA IN PATIENTS GIVEN MULTIPLE ORAL DOSES OF 500 AND 1000 MG DAILY

https://doi.org/10.1016/S1043661802002384Get rights and content

Abstract

The present study compares the pharmacokinetics of azithromycin in plasma, lung tissue, and bronchial washing after oral administration of 500 mg (standard dose) versus 1000 mg daily for 3 days. Samples were taken during surgery for lung resection at various time points up to 204 h after the last drug dose, and azithromycin levels were analyzed by HPLC method. Azithromycin was widely distributed within the lower respiratory tract; sustained concentrations of the drug were detectable at the last sampling time (204 h) in lung tissue and bronchial washing, with long terminal half-lives of 132.86 and 74.32 h at 500 mg daily and 133.32 and 70.5 h at 1000 mg daily, respectively. Doubling the drug dose resulted in a remarkable increase in lung area under the curve (AUC, 1318 hx μg g−1 vs 2502 hx μg g−1) and peak tissue concentration (9.13±0.53 μg g−1 vs 17.85±2.4 μg g−1). In addition to this, enhanced azithromycin penetration from plasma into bronchial secretion and lung tissue was evidenced by the increase in the ratio of AUCbronchial washing versus AUCplasma (2.96 vs 5.27 at 500 and 1000 mg, respectively) and AUClung versus AUCplasma (64.35 vs 97.73 at 500 and 1000 mg, respectively). In conclusion, the exposure of lung and bronchial washing to azithromycin is increased by doubling the dose, which results in favorable pharmacokinetic profile of the drug in the lower respiratory tract.

Section snippets

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

References (14)

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