Pharmacokinetics of oral azithromycin in serum, urine, polymorphonuclear leucocytes and inflammatory vs non-inflammatory skin blisters in healthy volunteers
Pharmacokinetics of oral azithromycin in serum, urine, polymorphonuclear leucocytes and inflammatory vs non-inflammatory skin blisters in healthy volunteers
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DOI：
10.2165/00044011-199815020-00009
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发表时间：
1998-02-01
影响因子：
3.2
通讯作者：
Forrest, A
中科院分区：
文献类型：
--
作者：
Ballow, CH;Amsden, GW;Forrest, A
进行了两项开放标签研究，以评估口服阿奇霉素 5 天疗程（总计 1500 毫克）的血清、尿液、多形核 (PMN) 和红细胞 (RBC) 药代动力学。还诱导了炎性和非炎性水泡，以研究阿奇霉素优先集中在模型感染部位的倾向。 14 名受试者参与了这两项研究，并且对阿奇霉素和研究方法耐受良好。血清和尿液数据的联合模型显示，其分布非常广泛到外周区室、肾清除率低（总口服清除率的 7%）和终末半衰期延长（79 小时）。最终剂量后 PMN 白细胞浓度达到峰值 119 mg/L，并在最终剂量后 7 天保持在 60 mg/L 以上。炎症性水疱 (2.2) 与非炎症性水疱 (1.2) 中水疱与血清 AUC 的比率显着较高 (p < 0.02)。阿奇霉素被中性粒细胞广泛吸收，加上阿奇霉素在炎症区室（例如感染部位）的积累，支持了这样的假设：携带阿奇霉素的中性粒细胞白细胞迁移到炎症部位，从而提高了局部浓度。这些研究进一步证明了阿奇霉素独特的药代动力学特性及其通过吞噬细胞优先递送至感染部位。
Two open-label studies were conducted to assess the serum, urine, poly morphonuclear (PMN) and red blood cell (RBC) pharmacokinetics of a 5-day course (1500mg total) of oral azithromycin. Inflammatory and non-inflammatory blisters were also induced to study the propensity of azithromycin to preferentially concentrate at a model infection site. 14 subjects participated in the two studies and tolerated azithromycin and the study methods well. Comodelling of the serum and urine data demonstrated very extensive distribution into peripheral compartments, low renal clearance (7% of total oral clearance) and an extended terminal half-life (79 hours). PMN leucocyte concentrations peaked at 119 mg/L following the final dose and remained above 60 mg/L 7 days after the final dose. The ratio of blister to serum AUCs was significantly higher in inflammatory (2.2) vs non-inflammatory (1.2) blisters (p < 0.02). The extensive uptake of azithromycin into PMNs coupled with the accumulation of azithromycin into an inflammatory compartment (e.g. infection site) support the hypothesis that PMN leucocytes laden with azithromycin migrate to sites of inflammation, thereby enhancing local concentrations. These studies further demonstrate the unique pharmacokinetic properties of azithromycin and its preferential delivery by phagocytes to the site of infection.