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 (Cmax, 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.
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 (Cmax, 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.
Authors: P Matzneller; S Krasniqi; M Kinzig; F Sörgel; S Hüttner; E Lackner; M Müller; M Zeitlinger Journal: Antimicrob Agents Chemother Date: 2013-01-28 Impact factor: 5.191
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Authors: Avraham Beigelman; Megan Isaacson-Schmid; Geneline Sajol; Jack Baty; Oscar M Rodriguez; Erin Leege; Kevin Lyons; Toni L Schweiger; Jie Zheng; Kenneth B Schechtman; Mario Castro; Leonard B Bacharier Journal: J Allergy Clin Immunol Date: 2014-11-18 Impact factor: 10.793
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Authors: Mythili Srinivasan; Leonard B Bacharier; Charles W Goss; Yanjiao Zhou; Jonathan Boomer; Sarah Bram; Dana Burgdorf; Carey-Ann Burnham; Timothy Casper; Mario Castro; Andrea Coverstone; Matthew Haslam; Watcharoot Kanchongkittiphon; Cadence Kuklinski; Qinghua Lian; Kenneth Schechtman; Gregory A Storch; Kelly True; Meghan A Wallace; Huiqing Yin-DeClue; Elizabeth Ahrens; Jinli Wang; Avraham Beigelman Journal: Contemp Clin Trials Commun Date: 2021-06-09