Ge Zhaohui, Wang Zili, Wei Mingji
Department of Orthopedic Surgery, Hospital of the Ningxia Medical School, Yinchuan, Ningxia, PR China.
Eur Spine J. 2008 Nov;17(11):1482-7. doi: 10.1007/s00586-008-0778-7. Epub 2008 Sep 16.
This is an experimental study on the distribution of antituberculosis drugs such as rifampin, isoniazid, and pyrazinamide in pathologic vertebrae of spinal tuberculosis in order to provide the regimen of chemotherapy and surgical treatment of spinal tuberculosis. The distribution of antituberculosis drugs in pathologic vertebral tissues matters greatly to the clinical effect of spinal tuberculosis' treatment. However, few pharmacokinetic studies and clinical reports about the concentrations of antituberculosis drugs in vertebral foci have been published so far. Twenty-four patients with spinal tuberculosis were divided into sclerotic group (n = 15) or non-sclerotic group (n = 9) according to radiographic features of lesion. All patients received chemotherapy with 2HRZ/2.5H(2)R(2)Z(2) for a duration of 4.5 months. Four weeks after chemotherapy all patients underwent surgery and the specimen of serum, ilium, and pathologic vertebral tissues, including sclerotic wall, subnormal osseous tissue, and foci were obtained during operation in 120-130 and 180-190 min after oral intake in the morning, respectively. The levels of three drugs in the specimen were measured using HPLC method. The concentration levels of isoniazid, rifampin and pyrazinamide varied greatly in different tissues of spinal tuberculosis, of which the bactericidal concentration values of isoniazid and rifampin and fivefold minimal inhibitory concentration (MICs) of pyrazinamide were found in subnormal vertebral bone and self-contrast ilium, the MICs of all drugs were found in sclerotic wall outside foci, and undetected level was found in foci inside the sclerotic wall. To patients without vertebral sclerotic wall around the foci, the isoniazid in foci was of bactericidal level and rifampin and pyrazinamide in foci corresponded to the MICs respectively. The sclerotic bone of affected vertebra plays an important role in blocking the antituberculosis drug's penetration into tuberculosis focus.
这是一项关于利福平、异烟肼和吡嗪酰胺等抗结核药物在脊柱结核病理椎体中分布情况的实验研究，目的是为脊柱结核的化疗和手术治疗方案提供依据。抗结核药物在病理椎体组织中的分布对脊柱结核的治疗临床效果至关重要。然而，目前关于椎体病灶中抗结核药物浓度的药代动力学研究和临床报道较少。24例脊柱结核患者根据病变的影像学特征分为硬化组（n = 15）和非硬化组（n = 9）。所有患者均接受2HRZ/2.5H(2)R(2)Z(2)化疗，疗程为4.5个月。化疗4周后所有患者接受手术，分别于上午口服药物后120 - 130分钟和180 - 190分钟手术时获取血清、髂骨及病理椎体组织标本，包括硬化壁、骨缺损区及病灶。采用高效液相色谱法测定标本中三种药物的含量。异烟肼、利福平和吡嗪酰胺在脊柱结核不同组织中的浓度水平差异很大，其中异烟肼和利福平的杀菌浓度值以及吡嗪酰胺的5倍最低抑菌浓度（MIC）在骨缺损区和自身对照髂骨中被发现，所有药物的MIC在病灶外的硬化壁中被发现，而在硬化壁内的病灶中未检测到。对于病灶周围无椎体硬化壁的患者，病灶中的异烟肼处于杀菌水平，病灶中的利福平和吡嗪酰胺分别相当于MIC。受累椎体的硬化骨在阻止抗结核药物渗入结核病灶方面起重要作用。
