骨水泥载万古霉素超声低频脉冲型治疗的起始时间对药动药效产生的影响分析

目的:研究低频脉冲超声治疗的起始时间对载万古霉素骨水泥的药物动力学、药效释放以及抗菌活性的影响。方法:选择50只健康大鼠,在大鼠髋关节均植入载万古霉素的骨水泥以及标准金黄色葡萄球菌(ATCC 13565,中国生物鉴定研究所),随后将50只大鼠随机分成观察组、对照组,观察组在植入后12 h进行低频超声治疗,对照组在植入后30 min进行低频超声治疗,两组均治疗12 h后取4只大鼠测定髋关节内的渗血量,其余大鼠测定髋关节内的药物浓度,计算药物动力及药效参数,在植入48 h后计数髋关节腔内的活菌量并进行组间比较。结果:观察组、对照组均在植入3 h后达到药物浓度高峰,对照组3 h后药物浓度呈明显的下降态势,并在14 h后下降到MIC以下,观察组在3 h后也呈下降态势,但在12 h采用低频超声治疗后,药物浓度再次上升,并一直持续在MIC以上至第34小时;观察组C_max/MIC(5.58±1.86)明显低于对照组的(14.81±2.41),差异具有统计学意义(P<0.05);观察组T_>mic(35.08±5.98)h明显高于对照组的(13.49±1.49)h,差异具有统计学意义(P<0.05);对照组菌落数、渗血量明显高于观察组(P<0.05)。结论:与植入后立即进行超声治疗相比,在第12小时进行治疗能够有效提高血液的T_>mic, 提高载万古霉素骨水泥的抗菌作用。

Effects of starting time of low frequency impulse ultrasound on clinical pharmacokinetics and pharmacodynamics of vancomycin-loaded bone cement

OBJECTIVE To study the effects of starting time of low frequency pulse ultrasound on pharmacokinetics, pharmacodynamics, and antibacterial activity of vancomycin loaded bone cement. METHODS A total of 50 healthy rats were selected, vancomycin loaded bone cement and standard Staphylococcus aureus strain (ATCC 13565, China Biology Identification Institute), and randomly divided into observation group and control group. Low frequency impulse ultrasonic therapy was administered 12 h after implantation in observation group and after 30 min in control group. After the animals were treated for 12 h, volume of capillary hemorrhage was determined in hip joints of 4 rats in each group. For the remaining rats, drug concentration was determined in hip joints. The pharmacokinetics and pharmacodynamic parameters were calculated. Viable organism was counted and compared in hip joint between different groups 48 h after implantation. RESULTS In observation group and control group, drug peak concentration was achieved since the third hour of implantation. Drug concentration in animals of control group declined obviously 3 h later, and below MIC 14 h later. In observation group, drug concentration also tended to decline, but after low frequency ultrasound at 12 h, drug concentration increased again to above MIC till 34h. In observation group, C_max/MIC (5.58±1.86) was significantly higher than control group (14.81±2.41) (P<0.05); in observation group, T_>mic (35.08±5.98) h was significantly higher than control group (13.49±1.49) h (P<0.05). In control group, colony count and volume of capillary hemorrhage were significantly higher than those in observation group (P<0.05). CONCLUSION Compared with rats treated with ultrasonic therapy immediately, ultrasonic therapy 12 hours later can effectively improve T_>mic of blood and the antibacterial activity of vancomycin loaded bone cement.