Shiraishi Y, Okajima M, Sai Y, Miyamoto K, Inaba H
Department of Emergency Medical Science, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Anaesth Intensive Care. 2012 May;40(3):442-9. doi: 10.1177/0310057X1204000309.
Pharmaceutical agents directed against methicillin-resistant Staphylococcus aureus can be eliminated during haemodiafiltration, not only by diffusion and ultrafiltration, but also by adsorption onto haemofilters. The latter may be affected by the binding of agents to serum albumin. The present study therefore investigated the affinity of anti-methicillin-resistant Staphylococcus aureus agents (teicoplanin, linezolid, vancomycin) for haemofilters and the pharmacokinetic properties of teicoplanin during haemodiafiltration. Linezolid, teicoplanin and vancomycin were first screened for their in vitro affinity for three different kinds of filter membranes: polysulfone, polyacrylonitrile and polymethylmethacrylate. Only teicoplanin showed significant filter-binding activity. An in vitro haemodiafiltration circulation model was then developed that incorporated a one-litre beaker containing Krebs-Ringer's bicarbonate solution with/without human albumin (0 or 3 g/dl) as an artificial plasma. Teicoplanin (initial concentration 50 µg/ml, representing the maximum plasma concentration (Cmax) resulting from a typical clinical dosage) was circulated throughout the beaker. Teicoplanin concentrations in the 'plasma' and ultrafiltrate were determined by high performance liquid chromatography. In the screening experiment, teicoplanin was predominantly adsorbed onto polysulfone and polymethylmethacrylate membranes. Furthermore, teicoplanin was primarily eliminated by adsorption onto these filters during in vitro haemodiafiltration. Albumin significantly reduced both haemodiafiltration clearance and the adsorption-dependent elimination, although there were complex but significant interactions between albumin and the filter membrane. Elimination of teicoplanin in an in vitro haemodiafiltration model was largely due to adsorption onto polysulfone and polymethylmethacrylate haemofilters. Future clinical studies should likely be designed to evaluate present recommendations of teicoplanin dosages in patients on haemodiafiltration.
针对耐甲氧西林金黄色葡萄球菌的药物在血液透析滤过过程中可能会被清除，不仅通过扩散和超滤，还会吸附到血液滤过器上。后者可能会受到药物与血清白蛋白结合的影响。因此，本研究调查了抗耐甲氧西林金黄色葡萄球菌药物（替考拉宁、利奈唑胺、万古霉素）对血液滤过器的亲和力以及替考拉宁在血液透析滤过过程中的药代动力学特性。首先筛选了利奈唑胺、替考拉宁和万古霉素对三种不同滤膜（聚砜、聚丙烯腈和聚甲基丙烯酸甲酯）的体外亲和力。只有替考拉宁表现出显著的滤膜结合活性。然后建立了一个体外血液透析滤过循环模型，该模型包含一个装有含/不含人白蛋白（0或3 g/dl）的 Krebs-Ringer 碳酸氢盐溶液的一升烧杯作为人工血浆。替考拉宁（初始浓度50 µg/ml，代表典型临床剂量产生的最大血浆浓度（Cmax））在整个烧杯中循环。通过高效液相色谱法测定“血浆”和超滤液中的替考拉宁浓度。在筛选实验中，替考拉宁主要吸附在聚砜和聚甲基丙烯酸甲酯膜上。此外，在体外血液透析滤过过程中，替考拉宁主要通过吸附到这些滤器上而被清除。白蛋白显著降低了血液透析滤过清除率和吸附依赖性清除，尽管白蛋白与滤膜之间存在复杂但显著的相互作用。在体外血液透析滤过模型中，替考拉宁的清除主要是由于吸附到聚砜和聚甲基丙烯酸甲酯血液滤过器上。未来的临床研究可能应设计用于评估目前对接受血液透析滤过的患者使用替考拉宁剂量的建议。
