Pharmacy Professional Services, Beaumont Hospital - Dearborn, Dearborn, MI, USA.
Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
Nephrol Dial Transplant. 2019 Oct 1;34(10):1766-1772. doi: 10.1093/ndt/gfy166.
Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis.
This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay.
Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h-∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported.
Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy.
先前的药代动力学研究表明，肾功能下降（包括接受肾脏替代治疗的患者）会导致血清厄他培南浓度升高。本研究评估了接受血液透析患者的厄他培南药代动力学参数。
这是一项前瞻性、单中心、开放标签研究，检查了 7 名接受血液透析的非感染住院患者单次静脉（IV）注射 1g 厄他培南的药代动力学。在厄他培南给药前和给药后 0.5、1、2、6、12 和 48 小时（h）采集血样。通过验证的液相色谱-质谱法测定厄他培南浓度。
静脉推注 1g 厄他培南后，血浆浓度下降相对较慢，平均消除半衰期（T1/2）为 19.3±6.6 h。所有受试者的血浆浓度相似，给药后最大平均血浆浓度为 343±48μg/ml。系统血浆清除率（CL）和稳态分布容积（Vss）的平均值±标准差（SD）分别为 2±0.5ml/min 和 3295±1187ml。0h-∞（AUCinf）的平均值±SD 值为 7494±1424 h•μg/ml。未观察到性别效应，也未报告严重不良事件。
血液透析患者的厄他培南半衰期延长。考虑到非肾清除率和高效血液透析预期的 70%清除率，血液透析后每周 3 次给予 1g 厄他培南可能产生具有潜在抗菌疗效的药代动力学充分暴露。需要进一步研究来评估这种延长疗程的剂量的临床疗效和安全性。
