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莫西沙星向肝组织的渗透。

Penetration of moxifloxacin into liver tissue.

机构信息

Department of General, Visceral, Vascular and Paediatric Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.

出版信息

Int J Antimicrob Agents. 2012 Jun;39(6):505-9. doi: 10.1016/j.ijantimicag.2012.01.022. Epub 2012 Apr 21.

Abstract

Moxifloxacin is considered for treatment of pyogenic liver abscesses as well as antibiotic prophylaxis in the case of hepatobiliary interventions. The aim of this study was to provide data on the pharmacokinetic (PK) profile of moxifloxacin in serum and liver tissue of patients undergoing liver resection due to primary or secondary tumours of the liver. Patients scheduled for liver resection (n=34) received moxifloxacin 400 mg at randomised time intervals prior to surgery. Blood and healthy liver tissue were sampled 1.5-26 h after administration of moxifloxacin. Immediately after centrifugation, plasma was separated, frozen and stored until analysis. In a subgroup of 19 patients, additional plasma specimens were obtained after 2, 4, 8, 12, 24, 36 and 48 h to assess the PK profile. PK parameters of moxifloxacin were calculated applying a two-compartment model. Median (interquartile range) PK parameters were as follows: peak concentration at the end of moxifloxacin infusion (C(max)), 6.0 mg/L (4.8-7.1 mg/L); area under the concentration-time curve extrapolated to infinity (AUC(0-∞)), 51.1 mgh/L (40.3-57.7 mgh/L); elimination half-life, 13.2h (11.0-14.1 h); volume of distribution at steady state (V(ss)), 138.7 L (102.7-168.5 L); and total body clearance (CL), 7.8 L/h (6.9-9.9L/h). Mean tissue concentrations were 9.13 mg/kg after 1.6-2.4 h, 7.62 mg/kg after 2.6-4.9h, 7.48 mg/kg after 5.6-10.0 h and 6.24 mg/kg after 22.9-26.5 h. Mean tissue:serum ratios were 2.9, 3.4, 5.0 and 12.3, respectively. The lowest tissue concentration found in the study at any time point was 2.8 mg/kg. In conclusion, moxifloxacin rapidly penetrates into the liver tissue where its concentration remains high following intravenous administration. Therefore, intravenously applied moxifloxacin might be used for the treatment of bacterial liver infections such as pyogenic liver abscess as well as in pre-operative prophylaxis.

摘要

莫西沙星被认为可用于治疗化脓性肝脓肿和肝胆介入治疗的抗生素预防。本研究的目的是提供莫西沙星在原发性或继发性肝脏肿瘤患者行肝切除术中的药代动力学(PK)特征的血清和肝组织数据。34 例接受肝切除术的患者随机间隔时间在手术前给予莫西沙星 400mg。莫西沙星给药后 1.5-26 小时采集血液和健康肝组织样本。莫西沙星给药后立即离心,分离血浆,冷冻并保存直至分析。在 19 例患者的亚组中,在 2、4、8、12、24、36 和 48 小时后获得额外的血浆样本以评估 PK 特征。应用双室模型计算莫西沙星的 PK 参数。莫西沙星的 PK 参数中位数(四分位距)如下:莫西沙星输注结束时的峰浓度(C(max)),6.0mg/L(4.8-7.1mg/L);浓度-时间曲线下面积外推至无穷大(AUC(0-∞)),51.1mgh/L(40.3-57.7mgh/L);消除半衰期,13.2h(11.0-14.1h);稳态分布容积(V(ss)),138.7L(102.7-168.5L);总清除率(CL),7.8L/h(6.9-9.9L/h)。1.6-2.4 小时后组织平均浓度为 9.13mg/kg,2.6-4.9 小时后为 7.62mg/kg,5.6-10.0 小时后为 7.48mg/kg,22.9-26.5 小时后为 6.24mg/kg。组织:血清比值分别为 2.9、3.4、5.0 和 12.3。在任何时间点,研究中发现的最低组织浓度为 2.8mg/kg。总之,莫西沙星迅速穿透肝组织,静脉给药后其浓度保持在较高水平。因此,静脉应用莫西沙星可用于治疗化脓性肝脓肿等细菌性肝感染,也可用于术前预防。

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