Department of Orthopedic and Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Spine (Phila Pa 1976). 2011 Sep 15;36(20):E1290-5. doi: 10.1097/BRS.0b013e31820beae3.
To detect drug concentration levels and metabolite using high-performance liquid chromatography.
To map concentration levels of three antituberculous drugs and two metabolites in the abnormal osseous tissues around the foci of patients with spinal tuberculosis.
Concentration levels of antituberculous drugs in the focus of spinal tuberculosis has been reported. However, the mapping of drugs distribution in different regions surrounding the foci of tuberculosis vertebrae remains unexplored, as well as the metabolite of the drugs.
Thirty-eight patients with spinal tuberculosis were assigned into sclerotic group (n = 13) and nonsclerotic group (n = 25) based on computed tomographic (CT) images. All patients received a chemotherapy 10 months with 2HRZE/8H(2)R(2)E(2). All patients received surgery after 4 weeks of chemotherapy. Samples of serum, ilium, and pathologic vertebral tissues, including the foci, sclerotic wall (if applicable), region I of abnormal osseous tissues (within 4 mm), and region II of abnormal osseous tissues (more than 4 mm) from the foci were collected during operation. Concentration levels and metabolite of three drugs were measured using high-performance liquid method for all samples. Differences of means within groups were evaluated by ANOVA and Dunnett post hoc. A significant levels was set at P < 0.05.
Concentration levels of drugs varied greatly in different regions of spinal tuberculosis vertebrae. Concentration levels of isoniazid and rifampin were higher than the effective bactericidal concentration (EBC) level and that of pyrazinamide was five times of the minimal inhibitory concentration in the region II of abnormal osseous tissues and the ilium of nonsclerotic group. Three drugs achieved EBC in the region I of abnormal osseous tissues in the nonsclerotic group but not in the sclerotic group. Except pyrazinamide no drugs and their metabolite were identified in the foci of the sclerotic group, whereas there is trace of drugs and their metabolite in the foci of the nonsclerotic group.
Three drugs resulted in an effective bactericidal concentration level in osseous tissues around the foci of spinal tuberculosis except the osseous tissues 4 mm surrounding the sclerotic wall. The results suggested that osseous tissues within 4 mm surrounding the sclerotic wall should be excised during the surgery.
采用高效液相色谱法检测药物浓度水平和代谢物。
绘制三种抗结核药物和两种代谢物在脊柱结核病灶周围异常骨组织中的浓度水平。
已报道了抗结核药物在脊柱结核病灶中的浓度水平。然而，药物在结核椎体周围不同区域的分布情况以及药物的代谢物仍未被探索。
根据计算机断层扫描（CT）图像，将 38 例脊柱结核患者分为硬化组（n=13）和非硬化组（n=25）。所有患者均接受 10 个月的 2HRZE/8H(2)R(2)E(2)化疗。所有患者在化疗 4 周后接受手术。手术中采集血清、髂骨和病变椎骨组织（包括病灶、硬化壁（如适用）、异常骨组织 I 区（4mm 内）和异常骨组织 II 区（4mm 外））的样本，采用高效液相法测定所有样本中三种药物的浓度水平和代谢物。组内均值差异采用方差分析和 Dunnett 事后检验进行评估。显著性水平设为 P<0.05。
抗结核药物在脊柱结核椎体的不同区域浓度水平差异较大。异烟肼和利福平的浓度水平高于有效杀菌浓度（EBC）水平，吡嗪酰胺在非硬化组异常骨组织 II 区和髂骨中的浓度水平是最小抑菌浓度的五倍。在非硬化组的异常骨组织 I 区，三种药物均达到 EBC，但在硬化组未达到。除吡嗪酰胺外，硬化组病灶中未检测到药物及其代谢物，而非硬化组病灶中则有药物及其代谢物的痕迹。
除了硬化壁周围 4mm 的骨组织外，三种药物在脊柱结核病灶周围骨组织中均达到有效杀菌浓度水平。结果提示，在手术中应切除硬化壁周围 4mm 范围内的骨组织。
