高剂量替加环素在感染性休克患者体内的药物监测及药代动力学
Pharmacokinetics and drug concentration monitoring of high-dose tigecycline in patients with septic shock
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摘要: 建立感染性休克患者替加环素检测方法，采用Ultimate AQ-C18色谱柱(3.0 mm×100 mm，3 μm)，流动相为含0.2%甲酸，5 mmol/L醋酸铵水溶液-乙腈，梯度洗脱方式，电喷雾离子化正离子扫描模式下，用于定量分析的离子对分别为m/z 586.4→513.3(替加环素)、m/z 338.2→296.0(利奈唑胺)。替加环素血药浓度在50.15~2 006 ng/mL范围内线性关系良好，批内、批间RSD均小于15%，稳定性良好。11名感染性休克患者高剂量给药替加环素后，药物在体内药峰浓度(cmax)和药时曲线下面积(AUC0-12 h)分别为(1.97±0.87)μg/mL和(9.10±3.58)mg·h/L。研究结果表明，多重耐药菌所致感染性休克患者给予高剂量替加环素后，虽给药剂量翻倍，较之于常规剂量给药的院内获得性肺炎重症患者其AUC数值并未明显增加，且略低于同等高剂量给药脓毒血症患者，未达到预期杀菌效果，这可能由于感染性休克患者高血流动力学加快药物清除速率，以及感染综合症导致毛细血管通透性增加联合间隙水肿，药物的分布容积增加有关。综上所述，推荐在多药耐药所致感染性休克患者中使用替加环素的推荐剂量区间应为150~200 mg，须对重症患者进行替加环素治疗药物浓度监测，并根据患者病程的不同阶段及时调整给药剂量。Abstract: This article established a method for the detection of tigecycline in patients with septic shock. The column was Ultimate AQ-C18(3. 0 mm × 100 mm, 3 μm). The mobile phase was water(0. 2% Formic acid, 5 mmol/L ammonium acetate)-acetonitrile, gradient elution, the ion transitions were performed under ESI positive model at m/z 586. 4→513. 3(tigecycline), m/z 338. 2→296. 0(linezolid). Calibration curves of tigecycline showed good linear regression in the range of(50. 15-2 006)ng/mL. The intra-day and inter-day RSD were below 15%. Plasma sample kept good stability. The cmax and AUC0-12 h of tigecycline in septic shock patients were(1. 97±0. 87)μg/mL and(9. 10±3. 58)mg ·h/L. The results showed that after giving high doses tigecycline to patients with septic shock caused by multidrug-resistant strains, the AUC was not significantly higher in severe nosocomial pneumonia patients with conventional doses, and lower than the AUC of sepsis patients at the same dose, did not achieve the desired bactericidal effect. Maybe with the high hemodynamics in septic shock patients increased tigecycline glomerular filtration, and systemic infection leads to increased capillary permeability combined with interstitial edema, so that the distribution of the drug volume increases. In combination with the above, it is recommended that the recommended dose range for tigecycline in patients with septic shock caused by multidrug-resistant strains should be between 150 and 200 mg, and the concentration of tigecycline in the critically ill patients should be monitored and patients in different stages of the disease in a timely manner to adjust the dose.
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Keywords:
- high-dose tigecycline /
- septic shock /
- therapeutic drug monitoring /
- pharmacokinetics
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