ICU, Latsion Burn Center, Thriasion Hospital, Athens, Greece.
J Antimicrob Chemother. 2012 Oct;67(10):2459-62. doi: 10.1093/jac/dks257. Epub 2012 Jul 12.
Available data on colistin pharmacokinetics in patients undergoing continuous renal replacement therapy (CRRT) are limited. Our aim was to study colistin pharmacokinetics in critically ill patients treated with colistin methane sulphonate for Gram-negative sepsis and undergoing continuous venovenous haemodiafiltration for acute renal failure.
Three patients were studied. The colistin methane sulphonate dose administered was at the discretion of the attending physician and was in all cases lower than that recommended for individuals with intact renal function. Colistin methane sulphonate was administered intravenously over 30 min, and blood samples were collected from each patient pre- and post-filter for the HPLC determination of colistin levels in serum before infusion, at 10, 60, 120, 240, 360, 480 and 600 min from the end of infusion, and immediately before the next dose. Concurrently, spot samples of effluent from the haemofilter were also collected and analysed. Both colistin total extracorporeal clearance and clearance in the effluent were calculated.
Extracorporeal clearance resulted in substantial removal of colistin (43%-59% of total colistin clearance). Total colistin clearance was found to be reduced (varying between 3.3 and 4.5 L/h), compared with patients with normal renal function. Colistin methane sulphonate dosage resulted in clearly suboptimal colistin steady-state concentrations.
In spite of substantial extracorporeal clearance, total colistin clearance was reduced, compared with patients with normal renal function. Colistin adsorption by the haemofilter contributed to its extracorporeal clearance to a large extent. Studies on other patients receiving colistin methane sulphonate and undergoing CRRT are required before more appropriate dosage regimens can be recommended.
目前关于连续性肾脏替代治疗（CRRT）患者中多粘菌素药代动力学的数据有限。我们的目的是研究多粘菌素甲磺酸治疗革兰氏阴性菌败血症的危重症患者，并进行连续性静脉-静脉血液滤过治疗急性肾功能衰竭时，多粘菌素甲磺酸的药代动力学。
共纳入 3 名患者。多粘菌素甲磺酸的剂量由主治医生决定，在所有情况下均低于肾功能正常个体的推荐剂量。多粘菌素甲磺酸经静脉输注 30 分钟，在输注结束前、输注后 10、60、120、240、360、480 和 600 分钟以及下一次给药前，从每位患者的预滤器和滤器后采集血样，用于 HPLC 测定血清中的多粘菌素水平。同时收集血液滤过器流出液的点样并进行分析。计算多粘菌素的总体外清除率和滤器中的清除率。
体外清除导致多粘菌素大量清除（占总多粘菌素清除率的 43%-59%）。与肾功能正常的患者相比，发现总多粘菌素清除率降低（在 3.3 至 4.5 L/h 之间变化）。多粘菌素甲磺酸的剂量导致多粘菌素稳态浓度明显不足。
尽管体外清除率很大，但与肾功能正常的患者相比，总多粘菌素清除率降低。血液滤器对多粘菌素的吸附在很大程度上促成了其体外清除。需要对接受多粘菌素甲磺酸和进行 CRRT 的其他患者进行研究，然后才能推荐更合适的剂量方案。
