Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA.
Clin J Am Soc Nephrol. 2011 May;6(5):1081-8. doi: 10.2215/CJN.08510910. Epub 2011 Mar 10.
This study sought to (1) characterize the pharmacokinetic (PK) profile of intravenous (i.v.) daptomycin among patients receiving continuous ambulatory peritoneal dialysis (CAPD); (2) identify optimal i.v. CAPD dosing schemes; and (3) determine extent of daptomycin penetration into the peritoneal space after i.v. administration.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A PK study was conducted among eight CAPD patients. Population PK modeling and Monte Carlo simulation (MCS) were used to identify CAPD dosing schemes providing efficacy and toxicity plasma profiles comparable with those obtained from MCS using the daptomycin population PK model derived from patients in the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. The primary efficacy exposure target was the area under the curve (AUC). For toxicity, the goal was to identify CAPD dosing schemes that minimized plasma trough concentrations in excess of 24.3 mg/L. Finally, peritoneal cavity penetration was determined.
Administration of i.v. daptomycin 4 or 6 mg/kg, depending on indication, every 48 h was identified as the optimal CAPD dosing scheme. This regimen provided cumulative (AUC(0-48)) and daily partitioned (AUC(0-24 h) and AUC(24-48 h)) plasma AUC values similar to the SAB-IE or "typical patient" simulations. In addition, the proportion of patients likely to experience an elevated trough concentration in excess of 24.3 mg/L was similar between every 48 h CAPD dosing and the referent group. Penetration into the peritoneal cavity was 6% of plasma.
Daptomycin 4 or 6 mg/kg, on the basis of indication, i.v. every 48 h was found to be the optimal i.v. CAPD dosing scheme.
本研究旨在：（1）描述接受持续非卧床腹膜透析（CAPD）的患者中静脉（i.v.）达托霉素的药代动力学（PK）特征；（2）确定最佳的 i.v. CAPD 给药方案；（3）确定 i.v. 给药后达托霉素渗透进入腹膜腔的程度。
设计、地点、参与者和测量：在 8 名 CAPD 患者中进行了 PK 研究。群体 PK 建模和蒙特卡罗模拟（MCS）用于确定 CAPD 给药方案，该方案提供的疗效和毒性血浆谱与使用从 SAB-IE 研究中的患者推导的达托霉素群体 PK 模型进行 MCS 获得的谱相当。主要疗效暴露目标是曲线下面积（AUC）。对于毒性，目标是确定最小化超过 24.3 mg/L 的血浆谷浓度的 CAPD 给药方案。最后，确定了腹膜腔的渗透情况。
根据适应证，每 48 小时静脉注射 4 或 6mg/kg 的达托霉素被确定为最佳的 CAPD 给药方案。该方案提供了累积（AUC（0-48））和每日分区（AUC（0-24 h）和 AUC（24-48 h））血浆 AUC 值与 SAB-IE 或“典型患者”模拟相似。此外，每 48 小时 CAPD 给药和参照组发生谷浓度超过 24.3 mg/L 的患者比例相似。渗透进入腹膜腔的比例为 6%的血浆。
基于适应证，每 48 小时静脉注射 4 或 6mg/kg 的达托霉素被发现是最佳的 i.v. CAPD 给药方案。
