肠内抗结核药物在需要重症监护的患者中的药代动力学。

The pharmacokinetics of enteral antituberculosis drugs in patients requiring intensive care.

机构信息

Department of Medicine, Stellenbosch University, Tygerberg, Western Cape, South Africa.

出版信息

S Afr Med J. 2013 Apr 5;103(6):394-8. doi: 10.7196/samj.6344.

DOI:10.7196/samj.6344

PMID:23725959

Abstract

BACKGROUND

There is a paucity of data on the pharmacokinetics of fixed-dose combination enteral antituberculosis treatment in critically ill patients.

OBJECTIVES

To establish the pharmacokinetic profile of a fixed-dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol given according to weight via a nasogastric tube to patients admitted to an intensive care unit (ICU).

METHODS

We conducted a prospective, observational study on 10 patients (mean age 32 years, 6 male) admitted to an ICU and treated for tuberculosis (TB). Serum concentrations of the drugs were determined at eight predetermined intervals over 24 hours by means of high-performance liquid chromatography.

RESULTS

The therapeutic maximum plasma concentration (Cmax) for rifampicin at time to peak concentration was achieved in only 4 patients, whereas 2 did not achieve therapeutic Cmax for isoniazid. No patient reached sub-therapeutic Cmax for pyrazinamide (6 were within and 4 above therapeutic range). Three patients reached sub-therapeutic Cmax for ethambutol, and 6 patients were within and 1 above the therapeutic range. Patients with a sub-therapeutic rifampicin level had a higher mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score (p=0.03) and a lower estimated glomerular filtration rate (GFR) (p=0.03).

CONCLUSIONS

A fixed-dose combination tablet, crushed and mixed with water, given according to weight via a nasogastric tube to patients with TB admitted to an ICU resulted in sub-therapeutic rifampicin plasma concentrations in the majority of patients, whereas the other drugs had a more favourable pharmacokinetic profile. Patients with a sub-therapeutic rifampicin concentration had a higher APACHE II score and a lower estimated GFR, which may contribute to suboptimal outcomes in critically ill patients. Studies in other settings have reported similar proportions of patients with 'sub-therapeutic' rifampicin concentrations.

摘要

背景

目前关于危重症患者固定剂量联合肠内抗结核治疗药代动力学的数据很少。

目的

通过鼻胃管给予危重症监护病房（ICU）患者体重标准化的利福平、异烟肼、吡嗪酰胺和乙胺丁醇固定剂量联合制剂，建立其药代动力学特征。

方法

我们对 10 例（平均年龄 32 岁，男性 6 例）入住 ICU 并接受结核病（TB）治疗的患者进行了一项前瞻性、观察性研究。通过高效液相色谱法在 24 小时内的 8 个预定时间间隔测定药物的血清浓度。

结果

只有 4 例患者在达峰时间达到了利福平的治疗最大血浆浓度（Cmax），而 2 例患者异烟肼未达到治疗 Cmax。没有患者的吡嗪酰胺达到亚治疗 Cmax（6 例在治疗范围内，4 例在治疗范围以上）。3 例患者的乙胺丁醇达到亚治疗 Cmax，6 例患者在治疗范围内，1 例患者在治疗范围以上。利福平水平低于治疗范围的患者，其急性生理学和慢性健康评估 II（APACHE II）评分均值更高（p=0.03），估算肾小球滤过率（eGFR）更低（p=0.03）。

结论

对于入住 ICU 的结核病患者，给予体重标准化的固定剂量联合片剂，粉碎后与水混合，通过鼻胃管给药，结果大多数患者的利福平血药浓度低于治疗范围，而其他药物具有更有利的药代动力学特征。利福平血药浓度低于治疗范围的患者，其 APACHE II 评分更高，eGFR 更低，这可能导致危重症患者的结局不佳。其他研究环境中也报告了类似比例的患者利福平浓度“低于治疗范围”。