Lovering A M, White L O, MacGowan A P, Reeves D S
Bristol Centre for Antimicrobial Research and Evaluation, Department of Medical Microbiology, Southmead Hospital, Westbury on Trym, UK.
J Antimicrob Chemother. 1996 Oct;38(4):599-604. doi: 10.1093/jac/38.4.599.
Rifampicin was absorbed onto gelatin-sealed (Gelsoft and Unigraft) or collagen-sealed (Hemashield) vascular grafts by soaking for 15 min in a 1000 mg/L solution. Bound drug was then eluted from the grafts by incubation in phosphate buffered saline (PBS) at 37 degrees C and at timed intervals the concentration of rifampicin remaining in the grafts was determined. Although all three grafts contained high concentrations of rifampicin immediately after absorption of drug, rifampicin concentrations rapidly fell during elution with PBS to approximately 1.25 mg/kg of graft after 5 h incubation in PBS, indicating that most of the rifampicin absorbed to the grafts was only loosely bound. However, once this loosely bound fraction had been removed there was a much slower elution of the remaining rifampicin from the grafts, suggesting a second and much more tightly bound fraction. The tightly bound fraction eluted with an apparent half-life of 47-76 h, depending on the graft, and extrapolation back to time zero from this phase suggests that only a very small amount of the rifampicin is tightly bound to the graft after initial soaking (0.6-1.3 mg/kg).
利福平通过在1000 mg/L溶液中浸泡15分钟被吸附到明胶密封(Gelsoft和Unigraft)或胶原密封(Hemashield)的血管移植物上。然后将结合的药物在37℃的磷酸盐缓冲盐水(PBS)中孵育从移植物中洗脱,并在不同时间间隔测定移植物中剩余的利福平浓度。尽管在药物吸收后所有三种移植物都含有高浓度的利福平,但在用PBS洗脱过程中,利福平浓度在PBS中孵育5小时后迅速下降至约1.25 mg/kg移植物,这表明吸附到移植物上的大部分利福平只是松散结合。然而,一旦去除了这种松散结合的部分,剩余的利福平从移植物中的洗脱速度要慢得多,这表明存在第二个且结合紧密得多的部分。紧密结合部分的洗脱表观半衰期为47 - 76小时,具体取决于移植物,从该阶段外推到时间零点表明,在初始浸泡后只有极少量的利福平紧密结合到移植物上(0.6 - 1.3 mg/kg)。