Mor N, Heifets L
National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
Antimicrob Agents Chemother. 1993 Jun;37(6):1380-2. doi: 10.1128/AAC.37.6.1380.
A single 2-h pulsed exposure of either human monocyte-derived macrophages or J774 cells infected with Mycobacterium avium to clarithromycin at 3.0 micrograms/ml completely inhibited the intracellular bacterial growth during the first four days of observation, and then only a slight increase in the number of CFU per milliliter took place between the fourth and seventh days. These data suggest that in vivo the intracellular bacteria can be effectively inhibited after a short period when the concentration of the drug in blood reaches its maximum. On the basis of these data, the assumptions that the elimination of bacteremia observed in clarithromycin clinical trials is a result of the activity of the drug not only against bacteria in blood but in macrophages as well and that the peak concentration attainable in blood is essential for these effects can be made.
将人单核细胞衍生的巨噬细胞或感染鸟分枝杆菌的J774细胞单次暴露于3.0微克/毫升的克拉霉素中2小时,在观察的前四天完全抑制了细胞内细菌的生长,然后在第四天至第七天之间每毫升CFU数量仅略有增加。这些数据表明,在体内,当血液中药物浓度达到最大值后的短时间内,细胞内细菌可被有效抑制。基于这些数据,可以做出以下假设:克拉霉素临床试验中观察到的菌血症消除不仅是药物对血液中细菌的作用,也是对巨噬细胞中细菌作用的结果,并且血液中可达到的峰值浓度对这些效应至关重要。