Roehr Anka C, Frey Otto R, Koeberer Andreas, Fuchs Thomas, Roberts Jason A, Brinkmann Alexander
1 Department of Pharmacy, Heidenheim General Hospital, Heidenheim - Germany.
Int J Artif Organs. 2015 Jan;38(1):17-22. doi: 10.5301/ijao.5000377. Epub 2015 Jan 23.
The main objective of this study was to investigate the clearance of 11 selected anti-infectives in an in vitro model of continuous veno-venous hemodialysis (CVVHD), in order to suggest rational dosing strategies for clinical practice.
Ceftazidime, ciprofloxacin, flucloxacillin, gentamicin, linezolid, meropenem, metronidazole, piperacillin, rifampicin, vancomycin and voriconazole were studied in two different solvents (sodium chloride 0.9% and HSA 5%) using a multifiltrate dialysis device by Fresenius Medical Care (Bad Homburg, Germany). For each solution, prefilter, postfilter, and dialysate samples were drawn simultaneously during one hour of dialysis and were assayed.
The clearance of all drugs except rifampicin in sodium chloride 0.9% was comparable (mean 1.76 ± 0.11 l/h). The clearance of these agents in human serum albumin solution 5% was reduced by between 5.3% and 72.2%. The unbound drug fraction correlated with a lower clearance in HSA 5% (Pearson correlation coefficient r = 0.933; p = 0.00008). No correlation between clearance in HSA 5% and the drugs' molecular weight was found (Pearson correlation coefficient r = 0.388; p = 0.268). Rifampicin was detected to bind to the surface of the polysulfone filter used. Dialysis clearance of ceftazidime, gentamicin, linezolid, meropenem, metronidazole, piperacillin and vancomycin during CVVHD accounted for over 25% of the total body clearance of population pharmacokinetic data for renally impaired patients.
The results from this study highlight that dose adaptations are needed for most of the drugs under investigation for patients undergoing CVVHD. In combination with polysulfone filters, rifampicin should be used with care in this setting.
本研究的主要目的是在持续静脉-静脉血液透析（CVVHD）体外模型中研究11种选定抗感染药物的清除率，以便为临床实践提出合理的给药策略。
使用德国费森尤斯医疗公司（巴特洪堡）的多聚滤过透析装置，在两种不同溶剂（0.9%氯化钠和5%人血清白蛋白）中研究头孢他啶、环丙沙星、氟氯西林、庆大霉素、利奈唑胺、美罗培南、甲硝唑、哌拉西林、利福平、万古霉素和伏立康唑。对于每种溶液，在透析1小时期间同时采集预滤器、后滤器和透析液样本并进行检测。
除利福平外，所有药物在0.9%氯化钠中的清除率相当（平均1.76±0.11升/小时）。这些药物在5%人血清白蛋白溶液中的清除率降低了5.3%至72.2%。游离药物分数与在5%人血清白蛋白中的较低清除率相关（Pearson相关系数r = 0.933；p = 0.00008）。未发现5%人血清白蛋白中的清除率与药物分子量之间存在相关性（Pearson相关系数r = 0.388；p = 0.268）。检测到利福平与所用聚砜滤器表面结合。CVVHD期间头孢他啶、庆大霉素、利奈唑胺、美罗培南甲硝唑、哌拉西林和万古霉素的透析清除率占肾功能受损患者群体药代动力学数据全身清除率的25%以上。
本研究结果突出表明，接受CVVHD的患者对大多数研究药物需要调整剂量。在与聚砜滤器联合使用时，在这种情况下应谨慎使用利福平。
