高效液相色谱法测定脊柱结核化疗后组织内利福平和去乙酰利福平的浓度

摘要

目的 研究正规化疗后脊柱结核病椎抗结核药物的分布特点,为脊柱结核化疗与手术方案的改进提供理论依据.方法将36例应用2SHRZ/6HRZ化疗方案结合手术治疗的脊柱结核患者按病灶有无硬化壁分为硬化骨组和非硬化骨组.化疗第4周手术,术晨服药后2h内取患者病椎组织、病椎组织外“亚健康骨”(距病灶边缘4 mm范围内、外“亚健康骨”分为A、B2段)、血浆及髂骨,采用高效液相色谱法测定上述样本的药物浓度.结果利福平(RFP)和去乙酰利福平(De-RFP)血药浓度高于髂骨、“亚健康骨”及病椎组织中的药物浓度；B段“亚健康骨”与髂骨内的RFP均达到了各自的杀菌浓度水平；A段“亚健康骨”在非硬化骨病例中的RFP均达到了各自的杀菌浓度,而在硬化骨病例中RFP却在最低抑菌浓度(MIC) 10倍以下；硬化骨病灶中的RFP浓度低于各药的最低抑菌浓度,药物浓度与A段“亚健康骨”相似,低于壁外围B段“亚健康骨”；而非硬化骨病灶中的RFP浓度仅为各药的最低抑菌浓度,低于外周A、B2段“亚健康骨”.结论RFP和De-RFP在脊柱结核患者正常骨与距病灶较远的“亚健康骨”中可达到有效治疗浓度,而在有硬化骨的病灶及邻近的“亚健康骨”中难以达到有效的药物浓度.在手术治疗脊柱结核彻底清除病灶的同时,应切除周围邻近的部分“亚健康骨”.%Abstract Objective To study the distribution of rifampin(RFP) and 25-desacetylrifampicin (De-RFP) in the lesions of spinal tuberculosis in order to provide theoretical evidence of chemotherapy and surgical treatment of spinal tuberculosis. Methods Thirty-six patients with spinal tuberculosis received chemotherapy of 2SHRZ/6HRZ (8 month totally). According to having sclerotic bones in the lesions or not,they were divided into sclerotic group (13 cases) and non-sclerotic group (23 cases). Four weeks after chemotherapy,all patients underwent surgery and specimen of serum,ilium and vertebral tissues and subnormal osseous tissue (divided into group A and B according to the distance from focus) were obtained within two hours after drug administration in the operation morning. The concentrations of RFP and its metabolites in the specimen were measured by HPLC. Results The serum concentrations of RFP and De-RFP were higher than that in the ilium,diseased vertebral tissue and subnormal osseous tissue. RFP concentrations in the ilium and subnormal bone tissue B reached or exceeded the bactericidal value. RFP concentration in subnormal bone tissue A reached or exceeded the bactericidal value in non-sclerotic group, but was ten-fold lower than its minimal inhibitory concentration (MIC) in sclerotic group. The drug concentration in lesions of sclerotic group was lower than its MIC and similar to that of subnormal bone tissue A,which was lower than that of subnormal bone tissue B. The RFP concentration in lesions of nonsclerotic group was equal to its MIC,which was lower than that of subnormal bone tissue A and B. Con-clusion The sclerotic bone of diseased vertebra plays an important role in blocking the drug's penetration into the tuberculotic focus, which results in much lower concentrations of the three drugs in lesions and adjacent subnormal bone tissues.