治疗药物监测可能会改善成年患者长期使用利奈唑胺治疗的安全性结局。
Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients.
机构信息
Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Department of Experimental and Clinical Medicine, Medical School, University of Udine, Udine, Italy.
出版信息
J Antimicrob Chemother. 2012 Aug;67(8):2034-42. doi: 10.1093/jac/dks153. Epub 2012 May 2.
OBJECTIVES
Prolonged treatment with linezolid may cause toxicity. The purpose of this study was to define pharmacodynamic thresholds for improving safety outcomes of linezolid.
METHODS
We performed a retrospective study of patients who had trough (C(min)) and peak (C(max)) plasma levels measured during prolonged linezolid treatment. Dosage adjustments were performed when C(min) ≥10 mg/L and/or AUC₂₄ ≥400 mg/L · h. Patients were divided into two subgroups according to the absence or presence of co-treatment with rifampicin (the linezolid group and the linezolid + rifampicin group, respectively). Data on demographic characteristics, disease, microbiology and haematochemical parameters were collected and outcomes in relation to drug exposure were compared between groups.
RESULTS
A total of 45 patients were included. Dosage adjustments were needed in 40% versus 0% of patients in the linezolid group (n = 35) versus the linezolid + rifampicin group (n = 10), respectively. Patients in the linezolid group had either significantly higher C(min) [3.71 mg/L (1.43-6.38) versus 1.37 mg/L (0.67-2.55), P < 0.001] or AUC₂₄ [212.77 mg/L · h (166.67-278.42) versus 123.33 mg/L · h (97.36-187.94), P < 0.001]. Thrombocytopenia appeared in 51.4% versus 0% of cases in the linezolid group versus the linezolid + rifampicin group, respectively. In 33.3% of those patients who were experiencing thrombocytopenia, therapeutic drug monitoring (TDM)-guided dosage reductions allowed recovery from toxicity and prosecution of therapy with good outcome. A logistic regression model for thrombocytopenia estimated a probability of 50% in the presence of C(min) of 6.53 mg/L and/or of AUC₂₄ of 280.74 mg/L · h.
CONCLUSIONS
Maintenance over time of C(min) between 2 and 7 mg/L and/or of AUC₂₄ between 160 and 300 mg/L · h may be helpful in improving safety outcomes while retaining appropriate efficacy in adult patients receiving prolonged linezolid treatment.
目的
利奈唑胺的长期治疗可能会导致毒性。本研究的目的是确定改善利奈唑胺安全性结果的药效学阈值。
方法
我们对接受利奈唑胺长期治疗期间进行了谷浓度（C（min））和峰浓度（C（max））血浆水平测量的患者进行了回顾性研究。当 C（min）≥10 mg/L 和/或 AUC₂₄≥400 mg/L·h 时，进行剂量调整。根据是否同时使用利福平（利奈唑胺组和利奈唑胺+利福平组），将患者分为两组。收集人口统计学特征、疾病、微生物学和血液化学参数的数据，并比较两组之间与药物暴露相关的结果。
结果
共纳入 45 例患者。在利奈唑胺组（n=35）和利奈唑胺+利福平组（n=10）中，分别有 40%和 0%的患者需要调整剂量。利奈唑胺组患者的 C（min）[3.71 mg/L（1.43-6.38）比 1.37 mg/L（0.67-2.55），P<0.001]或 AUC₂₄[212.77 mg/L·h（166.67-278.42）比 123.33 mg/L·h（97.36-187.94），P<0.001]明显更高。血小板减少症在利奈唑胺组中出现的比例为 51.4%，而在利奈唑胺+利福平组中为 0%。在经历血小板减少症的 33.3%患者中，治疗药物监测（TDM）指导的剂量减少允许毒性恢复，并继续进行治疗，取得良好结果。血小板减少症的逻辑回归模型估计 C（min）为 6.53 mg/L 和/或 AUC₂₄为 280.74 mg/L·h 时，血小板减少症的概率为 50%。
结论
在成年患者接受利奈唑胺长期治疗时，维持 C（min）在 2 至 7 mg/L 之间和/或 AUC₂₄在 160 至 300 mg/L·h 之间可能有助于提高安全性结果，同时保持适当的疗效。
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