腕关节结核病灶中二种抗痨药物浓度的测定及其临床意义

Determination of three anti-tuberculosis medicines in focus of patients with tuberculosis of the wrist and its clinical significance

目的研究腕关节结核病灶中抗结核药物的分布特点，为腕关节结核化疗与手术治疗方法的改进提供理论依据。方法32例应用3SHR（T）Z／6HR（T）方案化疗＋手术治疗的腕关节结核患者。按病变分为中心型和边缘型，以下分别简称Ⅰ组和Ⅱ组。化疗第4周手术，于术晨服药后2、4h两个时相点取Ⅰ组的硬化骨结核病变组织、亚正常骨结核病变组织和Ⅱ组的溶解骨结核病变组织、亚正常骨结核病变组织以及用高效液相色谱法测定上述样本药物浓度。结果（1）Ⅰ组和Ⅱ组中亚正常骨结核病变组织与溶解骨结核病变组织的INH和RFT均达到了各自最小杀菌浓度（MBCs）以上水平。（2）Ⅰ组中硬化骨结核病变组织的药物浓度仅为各药的最小抑菌浓度水平（MICs），远低于亚正常骨结核病变组织和溶解骨结核病变组织。结论INH、RFT在腕关节结核患者亚正常骨结核病变组织、溶解骨结核病变组织中可达到有效治疗浓度；而在硬化骨结核病变组织，远低于治疗浓度水平，硬化骨的存在成为抗结核化疗药物难于在骨结核病变组织内渗透的主要原因。

Objective To study the distribution of rifampicin, isoniazid in tissues of patients with tuberculosis wrist for the sake of providing given guide toward operation and postoperative chemotherapy. Methods 32 patients with tuberculosis wrist, according to radiographic data, were divided into Center group （ group Ⅰ） and Borderline groups （ group Ⅱ）. All patients received chemotherapy regimen of 3SHR（T） Z/6HR（T）. After treatment for 4 weeks, the patients＂ specimen of serum, and tuberculosis tissues （ groupⅠ） including sclerotic bone wall, sub-normal bone and tuberculosis tissues （ group Ⅱ） including dissolved bone wall, sub-normal bone were obtained during operation at 1, 2 hours respectively after oral medication. Then pretreatment and mensuration using HPLC method were carried out after specimen removal. Results Concentrations of isoniazid and rifapentine in （ group Ⅰ） and （ group Ⅱ） sub-normal bone and dissolved bone were above the minimal bactericidal concentration values. Concentration of 2 drugs in （ group Ⅰ） sclerotic bone wall were much lower than that in sub-normal bone and dissolved bone wall. Conclusion The concentration of 2 drugs in patient＇s sclerotic bone wall of wrist were too lower to eliminate the mycobacterium tuberculosis, while an effective concentration for anti-tuberculosis chemotherapy should be find in sub-normal bone and dissolved bone of wrist. Thus, the sclerotic bone of wrist plays an important role in obstructing the drug＇s penetration into tuberculosis.