Requirements for intracellular accumulation and release of clarithromycin and azithromycin by human phagocytes
Requirements for intracellular accumulation and release of clarithromycin and azithromycin by human phagocytes
复制标题
DOI：
10.1179/joc.1997.9.1.23
复制
发表时间：
1997-02-01
影响因子：
1.8
通讯作者：
Grassi, GG
中科院分区：
文献类型：
--
作者：
Fietta, A;Merlini, C;Grassi, GG
人多形核白细胞(PMN)、单核细胞和肺泡巨噬细胞对克拉霉素(CL)和阿奇霉素(AZ)摄取的测定表明，AZ的摄取水平高于CL。AZ的摄取动力学在18h内具有时间依赖性，而CL的摄取动力学类似于红霉素(ER)的摄取动力学，在孵育60min后达到最大掺入水平。细胞外抗生素浓度、中性粒细胞活力、细胞外钙离子、生理环境温度和pH对两种药物的积累均有影响。摄取不受细胞代谢抑制物或细胞膜激活剂的影响。去除细胞外抗生素后，AZ从PMN中的释放非常缓慢：培养24小时后，近50%的药物仍与细胞相关。佛波醇酯(PMA)刺激载药的PMN时，该衍生物的外流明显增强。CL释放动力学研究表明，该大环内酯类药物表现出类似ER的行为。然而，最初的细胞相关抗生素中约有10%表现出较长的保留时间。总体而言，这些数据表明，通过细胞膜的扩散和捕获到中性粒细胞的酸性隔间是CL和AZ摄取的重要事件。
Determination of clarithromycin (CL) and azithromycin (AZ) uptake by human polymorphonuclear leukocytes (PMNs), monocytes and alveolar macrophages showed that AZ achieved higher levels than CL. The uptake kinetics of AZ were time-dependent over an 18h period, while those of CL were similar to erythromycin (ER) kinetics, with a maximum level of incorporation being obtained after a 60 min incubation. The accumulation of both drugs was influenced by extracellular antibiotic-concentrations, PMN viability, extracellular calcium, physiological environmental temperature and pH. The uptake was not modified by inhibitors of cell metabolism or activators of cell membranes. After removal of extracellular antibiotic, the release of AZ from PMNs was very slow: nearly 50% of the drug remained cell-associated after 24h incubation. The efflux of this derivative was significantly enhanced when drug-loaded PMNs were stimulated by phorbol-myristate acetate (PMA). The kinetics of CL release indicated that this macrolide behaved like ER. Nevertheless, about 10% of the initial cell-associated antibiotic showed a prolonged retention. On the whole, these data suggest that diffusion through cell membranes and trapping into acidic compartments of PMNs are important events in CL and AZ uptake.