Surovoy Yury A, Burkin Maksim A, Galvidis Inna A, Sobolev Mikhail A, Rende Onur Can, Tsarenko Sergei V
I.I. Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia.
Faculty of Medicine, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia.
Eur J Clin Pharmacol. 2023 Jan;79(1):79-87. doi: 10.1007/s00228-022-03415-x. Epub 2022 Nov 15.
The aim of this study was to assess polymyxin B pharmacokinetics (PK) in patients with varying degrees of renal dysfunction and in patients who require continuous veno-venous hemodialysis (CVVHD).
The study enrolled 37 patients with sepsis, including 13 patients with glomerular filtration rate (GFR) below 80 mL/min and 11 patients on CVVHD. Each patient received a loading dose of polymyxin B (200-300 mg) and at least 3 subsequent doses of 100-150 mg every 12 h. For every patient, 6-8 blood samples were collected between doses. Polymyxin B (PMB) serum concentration was determined using enzyme-linked immunosorbent assay.
In sepsis, patients with preserved renal function mean area under the curve over 24 h (AUC0-24 h) value reached 67.8 ± 9.8 mgh/L, while in patients with GFR below 80 mL/min, mean AUC0-24 h was 87 ± 5.8 mgh/L. PMB PK in patients with renal insufficiency was characterized by significantly lower clearance (CL) compared to the normal renal function group (2.1 ± 0.1 L/h vs 3.9 ± 0.4 L/h respectively). In patients on CVVHD, mean AUC0-24 h was 110.4 ± 10.3 mg*h/L, while CL reached 2 ± 0.23 L/h. The median recovery rate from dialysate constituted 22%. Simulation of different dosage regimens that indicate a fixed maintenance dose of 100 mg q12h with a loading dose of 200 mg is optimal for patients on CVVHD, and no dosage increase is required.
This study demonstrates decreased clearance of PMB in patients with renal insufficiency, which puts them at risk of toxicity. Therefore, patients with extremes of renal function might benefit from therapeutic drug monitoring. For patients with anuria, who require CVVHD, we suggest a fixed dose of 100 mg q12h.
本研究旨在评估不同程度肾功能不全患者及需要持续静静脉血液透析（CVVHD）的患者中多粘菌素B的药代动力学（PK）。
该研究纳入了37例脓毒症患者，其中包括13例肾小球滤过率（GFR）低于80 mL/min的患者以及11例接受CVVHD的患者。每位患者接受一次多粘菌素B负荷剂量（200 - 300 mg），随后每12小时至少接受3次100 - 150 mg的剂量。对于每位患者，在给药间隔期间采集6 - 8份血样。使用酶联免疫吸附测定法测定多粘菌素B（PMB）血清浓度。
在脓毒症中，肾功能正常的患者24小时曲线下平均面积（AUC0 - 24 h）值达到67.8±9.8 mgh/L，而GFR低于80 mL/min的患者，平均AUC0 - 24 h为87±5.8 mgh/L。与肾功能正常组相比，肾功能不全患者的PMB药代动力学特征为清除率（CL）显著降低（分别为2.1±0.1 L/h和3.9±0.4 L/h）。在接受CVVHD的患者中，平均AUC0 - 24 h为110.4±10.3 mg*h/L，而CL达到2±0.23 L/h。透析液中的中位回收率为22%。不同给药方案的模拟表明，对于接受CVVHD的患者，100 mg q12h的固定维持剂量加200 mg的负荷剂量是最佳方案，无需增加剂量。
本研究表明肾功能不全患者中PMB的清除率降低，这使他们面临毒性风险。因此，肾功能极差的患者可能受益于治疗药物监测。对于需要CVVHD的无尿患者，我们建议100 mg q12h的固定剂量。
