利福平在脊柱结核患者不同组织分布的实验研究

An experimental study of rifampicin′s distribution in different tissues of spinal tuberculosis patients

目的:探讨脊柱结核患者应用利福平化疗时体内不同组织中的药物分布规律。方法:15例应用2SHRZ/3HRZ化疗方案+手术治疗的脊柱结核患者术前连续服药4周后手术,RFP每日顿服剂量为600mg,于术晨服药后120～130min、240～250min手术中分别取血浆、髂骨、病椎硬化骨、病椎非硬化骨、死骨及坏死干酪组织,采用高效液相色谱法测定样本中的药物浓度。结果:利福平的血药浓度最高,髂骨与椎体非硬化骨次之,死骨及坏死干酪组织则未检出利福平。被测组织中,硬化骨中利福平浓度仅为髂骨中的10%(P<0.05),病椎非硬化骨及自身对照髂骨的利福平浓度相近(P>0.05)。结论:利福平可在脊柱结核化疗强化期正常髂骨及病椎非硬化骨组织中达到有效杀菌浓度,而在硬化骨中仅相当于最低抑菌浓度,死骨及硬化包壳内的坏死干酪中基本无利福平分布。

Objective:To study rifampicin′s concentration in different tissues of patients with spinal tuberculosis undergoing chemotherapy.Method:High performance liquid chromatography was used to study pharmacokinetics of rifamcipin in 15 patients underwent chemotherapy regimen of 2SHRZ/3HRZ combination and operation.The dosage of rifamcipin was 600mg everyday for 4 weeks,afterward the patients′ specimen of serum,ilium and vertebrae including sclerotic bone,non-sclerotic bone and necrosis tissue were obtained during operation at 120～130 min and 240～250min respectively after oral medication.Result:Rifamcipin concentration was the highest in serum,followed by ilium and non-sclerotic bone of vertebrae,no rifamcipin was found in necrosis tissues.The concentration in ilium sclerotic bone of vertebrae was only 10 percent of that of ilium(P<0.05),and the concentration in non-sclerotic bone of vertebrae and ilium were nearly the same(P>0.05).Conclusion: The concentration of rifamcipin in the ilium and non-sclerotic bone of vertebrae exceed the minimal bactericidal concentration values during the intensive stage of chemotherapy,the drug concentration in sclerotic bone of vertebrae was approximate to Minimal inhibitory concentration values and there was nearly no drug distribution in necrosis tissues.