Comparative distribution of azithromycin in lung tissue of patients given oral daily doses of 500 and 1000 mg
Comparative distribution of azithromycin in lung tissue of patients given oral daily doses of 500 and 1000 mg
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DOI：
10.1093/jac/dkg138
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发表时间：
2003-04-01
影响因子：
5.2
通讯作者：
Campa, M
中科院分区：
文献类型：
--
作者：
Danesi, R;Lupetti, A;Campa, M
目的：根据抗菌药物的分布情况，优化抗菌药物的给药，增加药物暴露，达到根除细菌的目的。本研究检测了阿奇霉素在口服500毫克和1000毫克，每天1次，连续3天后患者血浆、肺组织和支气管洗涤中的药代动力学。患者和方法：在最后一次给药后204小时内，对48例开胸手术肺切除术患者进行血浆、肺组织和支气管洗涤取样，并测定抗生素浓度。结果：阿奇霉素在下呼吸道广泛分布，最后一次采样时肺组织中可检测到阿奇霉素的持续含量。抗生素剂量加倍导致曲线下肺面积（AUC, 1245.4 vs 2514.2 h × mg/kg）和峰值组织浓度（C-max, 8.93 +/- 2.05 vs 18.6 +/- 2.20 mg/kg）成比例增加。给药1000 mg后，肺组织中肺炎链球菌敏感株和中间株（MIC分别为0.5和2 mg/L）的药效学参数AUC/MIC比500 mg增加（AUC/MIC0.5 2414 vs 1144, AUC/ mic22112 vs 814.1 h × mg/kg）。结论：阿奇霉素剂量加倍后，肺部暴露量成比例增加，导致药物在下呼吸道的可预测药代动力学行为。
Objectives: The administration of antibacterial agents should be optimized on the basis of their distribution to enhance drug exposure and obtain bacterial eradication. This study examines the pharmacokinetics of azithromycin in plasma, lung tissue and bronchial washing in patients after oral administration of 500 mg versus 1000 mg once daily for 3 days.Patients and methods: Samples of plasma, lung tissue and bronchial washing were obtained from a cohort of 48 patients during open-chest surgery for lung resection up to 204 h after the last drug dose, and assayed for antibiotic concentrations.Results: Azithromycin was widely distributed within the lower respiratory tract and sustained levels of the drug were detectable at the last sampling time in lung tissue. Doubling the dose of the antibiotic resulted in a proportional increase in lung area under the curve (AUC, 1245.4 versus 2514.2 h x mg/kg) and peak tissue concentration (C-max, 8.93 +/- 2.05 versus 18.6 +/- 2.20 mg/kg). The pharmacodynamic parameter AUC/MIC for susceptible and intermediate strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L, respectively) increased after administration of the 1000 mg schedule compared with 500 mg (AUC/MIC0.5 2414 versus 1144 and AUC/MIC2 2112 versus 814.1 h x mg/kg, respectively) in pulmonary tissue.Conclusions: Lung exposure to azithromycin is increased proportionally by doubling the dose, which results in a predictable pharmacokinetic behaviour of the drug in the lower respiratory tract.