Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes
Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes
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DOI：
10.1086/507543
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发表时间：
2006-10-01
影响因子：
11.8
通讯作者：
van Crevel, Reinout
中科院分区：
文献类型：
--
作者：
Nijland, Hanneke M. J.;Ruslami, Rovina;van Crevel, Reinout
背景。 2 型糖尿病 (DM) 是结核病 (TB) 的一个重要危险因素，与结核病治疗反应较慢和死亡率较高有关。由于抗结核药物浓度较低可能是一个影响因素，因此我们比较了患有和不患有糖尿病的结核病患者中利福平的药代动力学。方法。在结核病治疗的持续阶段，17 名患有结核病和糖尿病的印度尼西亚成年患者以及 17 名年龄和性别匹配的结核病但无糖尿病患者被纳入该研究。所有患者均接受利福平 450 mg（10 mg/kg）和异烟肼 600 mg，每周 3 次。在服药后 0、2、4 和 6 小时评估利福平及其代谢物去乙酰利福平的稳态血浆浓度。结果。结核病合并糖尿病患者的利福平暴露几何平均值（AUC（0-6 h））为 12.3 mg x h/L（95% 置信区间 [CI]，8.0 - 24.2），仅结核病患者为 25.9 mg x h/L（95% CI，21.4 - 40.2）。利福平的最大浓度也发现了类似的差异。没有观察到利福平达到最大浓度的时间存在显着差异。与仅患有结核病的患者相比，患有结核病和糖尿病的患者中去乙酰利福平的 AUC（0-6 h）也低得多（几何平均值，0.60 vs. 3.2 mg x h/L；）。线性回归分析显示，较高的体重 (P < .001)、DM 的存在 (P = .06) 和血浆葡萄糖浓度 (P = .016) 与利福平暴露相关。结论。与患者相比，印度尼西亚结核病和糖尿病患者的利福平暴露量（AUC（0-6 小时））降低 53%
Background. Type 2 diabetes (DM) is a strong risk factor for tuberculosis (TB) and is associated with a slower response to TB treatment and a higher mortality rate. Because lower concentrations of anti-TB drugs may be a contributing factor, we compared the pharmacokinetics of rifampicin in patients with TB, with and without DM.Methods. Seventeen adult Indonesian patients with TB and DM and 17 age- and sex- matched patients with TB and without DM were included in the study during the continuation phase of TB treatment. All patients received 450 mg of rifampicin ( 10 mg/ kg) and 600 mg of isoniazid 3 times weekly. Steady- state plasma concentrations of rifampicin and its metabolite desacetylrifampicin were assessed at 0, 2, 4, and 6 h after drug intake.Results. Geometric means of rifampicin exposure ( AUC(0-6 h)) were 12.3 mg x h/ L ( 95% confidence interval [CI], 8.0 - 24.2) in patients with TB and DM, and 25.9 mg x h/L ( 95% CI, 21.4 - 40.2) in patients with TB only (). Similar differences were found for the maximum concentration of rifampicin. No significant differences in time to maximum concentration of rifampicin were observed. The AUC(0-6 h) of desacetylrifampicin was also much lower in patients with TB and DM versus patients with TB only ( geometric mean, 0.60 vs. 3.2 mg x h/L;). Linear regression analysis revealed that higher body weight (P < .001), the presence of DM (P = .06), and plasma glucose concentration (P = .016) were correlated with exposure to rifampicin.Conclusion. Exposure (AUC(0-6 h)) to rifampicin was 53% lower in Indonesian patients with TB and DM, compared with patients