Le Floch R, Arnould J-F, Vinsonneau C, Hovsepian L, Stephanazzi J, Bret P, Birraux G, Lovering A M
Centre de traitement des brûlés, CHU de Nantes, 44093 Nantes cedex 1, France.
Pathol Biol (Paris). 2010 Apr;58(2):e27-31. doi: 10.1016/j.patbio.2009.07.025. Epub 2009 Oct 24.
The aims of this multicentre open-label study was to evaluate the pharmacokinetics of linezolid in patients with burn injury above 20 % BSA and to compare them with healthy volunteers, matched in age, sex and weight. After a single 600 mg IV dose of linezolid, multiple blood and urine samples were taken from subjects, in order to determine linezolid concentrations, using a HPLC assay. C(max) and volume of distribution at steady state were not different between the two groups. Values describing clearance were altered in burns, leading to a reduction by half in AUC in these patients (42.5 versus 98.1 mghL(-1)). The enhancement of clearance was due to which of non renal clearance (323+/-191 versus 80.4+/-27.5 mLmin(-1)). We conclude that pharmacokinetics of linezolid are altered in burn patients, in a magnitude sufficient that linezolid concentration may be subtherapeutic in some patients and we suggest that the dosage interval may need to be decreased in this patient population.
这项多中心开放标签研究的目的是评估利奈唑胺在烧伤面积超过20%体表面积的患者中的药代动力学,并将其与年龄、性别和体重相匹配的健康志愿者进行比较。在单次静脉注射600mg利奈唑胺后,从受试者采集多个血液和尿液样本,以便使用高效液相色谱法测定利奈唑胺浓度。两组之间的C(max)和稳态分布容积没有差异。描述清除率的值在烧伤患者中发生改变,导致这些患者的AUC降低一半(42.5对98.1mg·h/L(-1))。清除率的提高归因于非肾清除率(323±191对80.4±27.5mL·min(-1))。我们得出结论,烧伤患者中利奈唑胺的药代动力学发生改变,改变程度足以使一些患者的利奈唑胺浓度低于治疗水平,我们建议在该患者群体中可能需要缩短给药间隔。