Pharmacokinetics of azithromycin in lung tissue, bronchial washing, and plasma in patients given multiple oral doses of 500 and 1000 mg daily

被引:38
作者
Di Paolo, A
Barbara, C
Chella, A
Angeletti, CA
Del Tacca, M
机构
[1] Univ Pisa, Dept Oncol Transplants & Adv Technol Med, Div Pharmacol & Chemotherapy, I-56126 Pisa, Italy
[2] Univ Pisa, CardioThorac Dept, Div Thorac Surg, Pisa, Italy
关键词
azithromycin; HPLC assay; lung; bronchial washing; plasma; pharmacokinetics;
D O I
10.1016/S1043661802002384
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mug g(-1) vs 2502 hx mug g(-1)) and peak tissue concentration (9.13 +/- 0.53 mug g(-1) vs 17.85 +/- 2.4 mug 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 AUC(bronchial) (washing) versus AUC(plasma) (2.96 vs 5.27 at 500 and 1000 mg, respectively) and AUC(lung) versus AUC(plasma) (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. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:545 / 550
页数:6
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