Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters
Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters
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DOI：
10.1128/aac.01067-15
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发表时间：
2015-12-01
影响因子：
4.9
通讯作者：
Romano-Moreno, S.
中科院分区：
文献类型：
--
作者：
Medelln-Garibay, S. E.;Cortez-Espinosa, N.;Romano-Moreno, S.
由于 2 型糖尿病 (T2DM) 发病率不断增加，结核病 (TB) 仍然是一个主要的公共卫生问题，这加剧了结核病的临床病程并增加了长期不良结果的风险。本研究的目的是表征结核病和 T2DM 患者中利福平 (RIF) 的药代动力学及其与生化和免疫学参数的关系。在进行 RIF 药代动力学评估的同一天评估生化和免疫学参数。在 TB-T2DM 组（主要存在营养不良）或 TB 组中未检测到与 T2DM 患者特有的代谢综合征相关的因素。与健康志愿者相比，TB 和 TB-T2DM 患者的 CD8(+) T 淋巴细胞和 NK 细胞百分比减少，肿瘤坏死因子 α (TNF-α) 水平较高，白细胞介素 17 (IL-17) 水平较低。在 TB 和 TB-T2DM 患者中观察到 RIF 吸收延迟；由于血糖控制不佳，后一组的吸收较差且较慢。糖尿病患者的 RIF 清除速度也较慢，从而延长了 RIF 的平均停留时间。 TB-T2DM 患者的血糖控制、TNF-α 血清浓度升高和 RIF 药代动力学之间存在显着相关性。当结核病和 T2DM 同时存在时，这些代谢和免疫状况的改变可能是抗结核治疗管理中需要考虑的因素。
Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-alpha) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-alpha serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.