Lim Sin Yin, Lewis Teresa, Woo Sukyung, Turman Martin, Bourne David W A, Burton Michael E, Rianthavorn Pornpimol
J Pediatr Pharmacol Ther. 2021;26(2):123-132. doi: 10.5863/1551-6776-26.2.123. Epub 2021 Feb 15.
Children who undergo hemodialysis (HD) and peritoneal dialysis are at increased risk of infection. Daptomcyin is used to treat resistant infections; however, the pharmacokinetics of daptomycin in pediatric and adolescent dialysis patients remain unknown.
We report the safety and pharmacokinetics of a single intravenous 5 mg/kg dose of daptomycin for 6 individuals age 12 to 17 years old who underwent HD or continuous cycling peritoneal dialysis (CCPD). Daptomycin concentrations from all samples were determined by high-performance liquid chromatography. A non-compartmental analysis was performed to compare the pharmacokinetic parameters among HD and CCPD patients. A population pharmacokinetic model was developed to describe the concentration-time profiles of daptomycin in plasma, urine, and dialysis effluent. Monte Carlo simulations were performed to assess the pharmacodynamic outcomes.
All subjects tolerated the single dose of daptomycin. During HD, significant drug removal was observed, compared with CCPD (26% vs 5% of total dose). A low daptomycin renal clearance (<12% of total clearance) with moderate variability (40.5%) was observed among subjects with residual renal function. An anuric and obese subject who received CCPD treatment appeared to have >80% higher daptomycin area under the plasma concentration-time curve than the other CCPD subjects. Dosing regimens that achieved predefined pharmacodynamic targets were reported.
Daptomycin clearance was faster in 12- to 17-year-old patients receiving HD than CCPD. Administration of daptomycin immediately after HD reduces drug loss. The CCPD treatment, anuria, and obesity may increase the risk for drug accumulation. Our pharmacokinetic model can be further used to optimize dosing regimens of daptomycin in this population.
接受血液透析（HD）和腹膜透析的儿童感染风险增加。达托霉素用于治疗耐药感染；然而，达托霉素在儿科和青少年透析患者中的药代动力学仍不清楚。
我们报告了6名年龄在12至17岁接受HD或持续循环腹膜透析（CCPD）的个体静脉注射单次5mg/kg剂量达托霉素的安全性和药代动力学。通过高效液相色谱法测定所有样本中的达托霉素浓度。进行非房室分析以比较HD和CCPD患者之间的药代动力学参数。建立群体药代动力学模型以描述达托霉素在血浆、尿液和透析流出液中的浓度-时间曲线。进行蒙特卡洛模拟以评估药效学结果。
所有受试者均耐受单次剂量的达托霉素。在HD期间，与CCPD相比，观察到显著的药物清除（分别为总剂量的26%和5%）。在有残余肾功能的受试者中观察到达托霉素肾清除率较低（<总清除率的12%）且变异性中等（40.5%）。一名接受CCPD治疗的无尿肥胖受试者的达托霉素血浆浓度-时间曲线下面积似乎比其他CCPD受试者高80%以上。报告了达到预定义药效学目标的给药方案。
在12至17岁接受HD的患者中，达托霉素清除率比CCPD更快。HD后立即给予达托霉素可减少药物损失。CCPD治疗、无尿和肥胖可能增加药物蓄积风险。我们的药代动力学模型可进一步用于优化该人群中达托霉素的给药方案。
