Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Parkville, Victoria 3052, Australia.
J Antimicrob Chemother. 2015;70(6):1804-11. doi: 10.1093/jac/dkv031. Epub 2015 Feb 18.
Colistin, administered intravenously as its inactive prodrug colistin methanesulphonate (CMS), is being increasingly used. However, there is very limited information available on the impact of haemodialysis (HD) on the pharmacokinetics of CMS and formed colistin.
A single 30 min intravenous dose of CMS (150 mg of colistin base activity) was administered to 10 patients undergoing HD. HD was performed from 1.5 to 5.5 h after the start of the CMS infusion. Serial blood samples were collected over 50 h, additional blood samples pre- and post-dialysis membrane at three timepoints during HD, dialysate samples at four timepoints during HD, and a cumulative urine sample over 24 h. CMS and colistin were determined by HPLC. Population modelling and determination of HD clearance by multiple methods was conducted.
The average amount of CMS recovered in the dialysate was 30.6% of the dose administered. The concentrations of CMS and colistin in the plasma and the amounts of CMS recovered in the dialysate were well described by the population disposition model. The clearance of CMS by dialysis as estimated by population analysis based on systemic plasma concentrations and amounts in the dialysate was 4.26 L/h (26% coefficient of variation). The dialysis clearance determined from the pre- and post-membrane plasma concentrations was 5.67 L/h (21%) for CMS and 3.99 L/h (44%) for colistin. Thus, CMS clearance by dialysis from trans-cartridge extraction was ∼30% higher than when calculated based on the amount in dialysate, suggesting adsorption to the membrane.
Due to the extensive removal of CMS by dialysis, HD should be conducted at the end of a dosing interval and a supplemental dose should be administered.
多黏菌素经静脉注射给药，以其无活性前体多黏菌素甲磺酸盐（CMS）的形式使用，应用越来越广泛。然而，关于血液透析（HD）对 CMS 和形成的多黏菌素药代动力学的影响，信息非常有限。
10 例接受 HD 的患者单次静脉滴注 30 分钟 CMS（150 毫克多黏菌素碱活性）。在 CMS 输注开始后 1.5 至 5.5 小时进行 HD。在 HD 期间的三个时间点采集透析前和透析膜后以及透析液样本，在 HD 期间的四个时间点采集透析液样本，在 24 小时内采集累积尿液样本。通过 HPLC 测定 CMS 和多黏菌素。进行了群体建模和通过多种方法确定 HD 清除率。
在透析液中回收的 CMS 量平均为给予剂量的 30.6%。CMS 和多黏菌素在血浆中的浓度以及在透析液中回收的 CMS 量，由群体处置模型很好地描述。根据基于系统血浆浓度和透析液中量的群体分析，透析对 CMS 的清除率为 4.26 L/h（26%变异系数）。从透析前和透析后血浆浓度确定的透析清除率，CMS 为 5.67 L/h（21%），多黏菌素为 3.99 L/h（44%）。因此，从跨膜提取透析清除 CMS 的速率比根据透析液中的量计算的速率高约 30%，这表明 CMS 吸附在膜上。
由于 CMS 被透析广泛清除，HD 应在给药间隔结束时进行，并应给予补充剂量。
