Majcher-Peszynska J, Haase G, Sass M, Mundkowski R, Pietsch A, Klammt S, Schareck W, Drewelow B
Center of Pharmacology and Toxicology, Institute of Clinical Pharmacology, University of Rostock, Schillingallee 70, 18057 Rostock, Germany.
Eur J Clin Pharmacol. 2008 Nov;64(11):1093-100. doi: 10.1007/s00228-008-0531-5. Epub 2008 Jul 25.
Physiological changes and local and systemic inflammation may affect plasma and tissue pharmacokinetics of antimicrobial agents in diabetics. The aim of the study was to investigate the penetration of linezolid into inflamed areas of infected diabetic foot wounds and the pharmacokinetics in the risk population of diabetics.
Pharmacokinetics and tissue penetration of linezolid into inflamed diabetic foot infection (DFI) tissue were determined at steady state in 15 patients with diabetes type 2 and DFI following administration of multiple oral doses of 600 mg given every 12 h. Second debridement was performed on days 4-6, 3 h after linezolid administration. Linezolid concentrations were determined in perinecrotic wound tissue of inflamed diabetic foot by high-performance liquid chromatography (HPLC).
A mean maximum plasma concentration (C(max)) in plasma of 14.3 mg/L was attained at a median of 2.0 h [time to reach C(max) (T(max)) range 0.5-6.0 h). Area under the concentration time curve from zero to 12 h (AUC(0-12 h)) with a mean of 114.1 mgh/L and C(min) of 5.4 mg/L were achieved in patients with diabetes mellitus type 2. Penetration of linezolid into inflamed areas of DFI with tissue/plasma ratios of mean 101.7% [95% confidence interval (CI) 56; 148%] produced a mean concentration of 9.6 microg/g (95% CI 7.4; 11.8 microg/g) greater than those predicted to be effective against methicillin-resistant staphylococci [minimum concentration that inhibits 90% of organisms (MIC(90)) of 4 mg/L]. Tissue/plasma ratios correlated positive with systemic inflammation.
Plasma pharmacokinetics of linezolid in diabetics and adequate levels in inflamed areas of diabetic foot wound suggest that an oral dose of 600 mg bd of linezolid provides effective concentrations for treating methicillin-resistant Staphylococcus aureus (MRSA) in DFI.
生理变化以及局部和全身炎症可能会影响糖尿病患者对抗菌药物的血浆和组织药代动力学。本研究的目的是调查利奈唑胺在感染性糖尿病足伤口炎症区域的渗透情况以及在糖尿病风险人群中的药代动力学。
在15例2型糖尿病合并糖尿病足感染（DFI）患者中，每12小时口服600毫克多次给药后，在稳态下测定利奈唑胺在炎症性糖尿病足感染（DFI）组织中的药代动力学和组织渗透情况。在第4 - 6天，利奈唑胺给药3小时后进行第二次清创术。通过高效液相色谱法（HPLC）测定炎症性糖尿病足坏死周围伤口组织中的利奈唑胺浓度。
血浆中平均最大浓度（C(max)）为14.3毫克/升，中位达峰时间（T(max)）为2.0小时（达峰时间范围为0.5 - 6.0小时）。2型糖尿病患者从零至12小时的浓度 - 时间曲线下面积（AUC(0 - 12 h)）平均为114.1毫克·时/升，C(min)为5.4毫克/升。利奈唑胺在DFI炎症区域的渗透情况，组织/血浆比值平均为101.7%[95%置信区间（CI）56；148%]，产生的平均浓度为9.6微克/克（95%CI 7.4；11.8微克/克），高于预计对耐甲氧西林葡萄球菌有效的浓度[抑制90%菌株的最低浓度（MIC(90)）为4毫克/升]。组织/血浆比值与全身炎症呈正相关。
利奈唑胺在糖尿病患者中的血浆药代动力学以及在糖尿病足伤口炎症区域的足够水平表明，口服剂量600毫克每日两次的利奈唑胺可为治疗DFI中的耐甲氧西林金黄色葡萄球菌（MRSA）提供有效浓度。
