利奈唑胺在不同体重健康志愿者中的即刻血液学毒性：一项 I 期临床试验。
Immediate hematological toxicity of linezolid in healthy volunteers with different body weight: a phase I clinical trial.
机构信息
Department of Clinical Pharmacology, PLA General Hospital, Beijing, PR China.
出版信息
J Antibiot (Tokyo). 2012 Apr;65(4):175-8. doi: 10.1038/ja.2011.142. Epub 2012 Jan 25.
Linezolid is an important therapeutic option for infections from multi-drug resistant Gram-positive pathogens. However, prolonged linezolid treatment (>14 days) is considered to increase the risk of hematological adverse events. We aimed to evaluate the hematological safety profile of an i.v. single dose of linezolid in healthy volunteers of different body weight. We conducted a phase I clinical trial involving 20 healthy male Chinese volunteers that received an i.v. single dose of linezolid (600 mg). The study participants were assigned to two groups: low-weight (LW) group: 50 kg <body weight ≤55 kg and high-weight (HW) group: ≥80 kg. A significant decrease in the hemoglobin (Hb) levels and red blood cell (RBC) count was observed at the end of administration of the study drug in both groups. White blood cell (WBC) count was simultaneously decreased in the HW group. In the LW group, Hb levels and RBC count were also significantly decreased at 5, 7 and 24 h. In the HW group, both values were significantly decreased at 5 h. At 48 h all values were normal. The observed decreases were numerically higher in the LW group compared with the HW group. Yet, no statistical significance was noted. No difference was observed in the platelet count in both the groups. Our findings suggest that linezolid-associated hematological toxicity may also occur shortly after the i.v. administration of the drug in both LW and HW healthy volunteers. Early initiated continuous monitoring of hematological values and linezolid dosage adjustment for body weight are recommended.
利奈唑胺是治疗多重耐药革兰阳性病原体感染的重要治疗选择。然而，长期使用利奈唑胺（>14 天）被认为会增加血液学不良事件的风险。我们旨在评估不同体重的健康志愿者单次静脉注射利奈唑胺的血液学安全性。我们进行了一项涉及 20 名健康男性中国志愿者的 I 期临床试验，他们接受了单次静脉注射利奈唑胺（600mg）。研究参与者被分为两组：低体重（LW）组：50kg<体重≤55kg 和高体重（HW）组：≥80kg。在两组中，在研究药物给药结束时观察到血红蛋白（Hb）水平和红细胞（RBC）计数明显下降。白细胞（WBC）计数同时在 HW 组中下降。在 LW 组中，Hb 水平和 RBC 计数在 5、7 和 24 小时也明显下降。在 HW 组中，这两个值在 5 小时时明显下降。在 48 小时时所有值均正常。与 HW 组相比，LW 组的观察值下降幅度更大，但无统计学意义。两组的血小板计数无差异。我们的发现表明，在 LW 和 HW 健康志愿者中，静脉注射利奈唑胺后不久也可能发生与利奈唑胺相关的血液学毒性。建议早期开始连续监测血液学值，并根据体重调整利奈唑胺剂量。
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