Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands
Department of Intensive Care, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
J Antimicrob Chemother. 2014 Dec;69(12):3294-9. doi: 10.1093/jac/dku313. Epub 2014 Aug 19.
Caspofungin is used for treatment of invasive fungal infections. As the pharmacokinetics (PK) of antimicrobial agents in critically ill patients can be highly variable, we set out to explore caspofungin PK in ICU patients.
ICU patients receiving caspofungin were eligible. Patients received a loading dose of 70 mg followed by 50 mg daily (70 mg if body weight >80 kg); they were evaluable upon completion of the first PK curve at day 3. Additionally, daily trough samples were taken and a second PK curve was recorded at day 7. PK analysis was performed using a standard two-stage approach.
Twenty-one patients were evaluable. Median (range) age and body weight were 71 (45-80) years and 75 (50-99) kg. PK sampling on day 3 (n = 21) resulted in the following median (IQR) parameters: AUC0-24 88.7 (72.2-97.5) mg·h/L; Cmin 2.15 (1.40-2.48) mg/L; Cmax 7.51 (6.05-8.17) mg/L; V 7.72 (6.12-9.01) L; and CL 0.57 (0.54-0.77) L/h. PK sampling on day 7 (n = 13) resulted in AUC0-24 107.2 (90.4-125.3) mg·h/L, Cmin 2.55 (1.82-3.08) mg/L, Cmax 8.65 (7.16-9.34) mg/L, V 7.03 (5.51-7.73) L and CL 0.54 (0.44-0.60) L/h. We did not identify any covariates significantly affecting caspofungin PK in ICU patients (e.g. body weight, albumin, liver function). Caspofungin was well tolerated and no unexpected side effects were observed.
Caspofungin PK in ICU patients showed limited intraindividual and moderate interindividual variability, and caspofungin was well tolerated. A standard two-stage approach did not reveal significant covariates. Our study showed similar caspofungin PK parameters in ICU patients compared with non-critically ill patients.
卡泊芬净用于治疗侵袭性真菌感染。由于重症患者的抗菌药物药代动力学（PK）可能高度可变，因此我们着手探索 ICU 患者的卡泊芬净 PK。
符合条件的 ICU 患者接受卡泊芬净治疗。患者接受 70mg 的负荷剂量，然后每天 50mg（体重>80kg 时为 70mg）；在第 3 天完成第一次 PK 曲线时可进行评估。此外，每天采集谷浓度样本并在第 7 天记录第二次 PK 曲线。PK 分析采用标准两阶段方法进行。
21 名患者可评估。中位（范围）年龄和体重分别为 71（45-80）岁和 75（50-99）kg。第 3 天（n=21）的 PK 采样得出以下中位（IQR）参数：AUC0-24 88.7（72.2-97.5）mg·h/L；Cmin 2.15（1.40-2.48）mg/L；Cmax 7.51（6.05-8.17）mg/L；V 7.72（6.12-9.01）L；CL 0.57（0.54-0.77）L/h。第 7 天（n=13）的 PK 采样得出 AUC0-24 107.2（90.4-125.3）mg·h/L，Cmin 2.55（1.82-3.08）mg/L，Cmax 8.65（7.16-9.34）mg/L，V 7.03（5.51-7.73）L 和 CL 0.54（0.44-0.60）L/h。我们没有发现任何对 ICU 患者卡泊芬净 PK 有显著影响的协变量（例如体重、白蛋白、肝功能）。卡泊芬净耐受性良好，未观察到意外的副作用。
卡泊芬净在 ICU 患者中的 PK 表现出有限的个体内和中等的个体间变异性，且卡泊芬净耐受性良好。标准两阶段方法未发现显著的协变量。与非重症患者相比，我们的研究显示 ICU 患者的卡泊芬净 PK 参数相似。
