Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea.
Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
J Crit Care. 2023 Dec;78:154402. doi: 10.1016/j.jcrc.2023.154402. Epub 2023 Aug 25.
To evaluate the population pharmacokinetics and pharmacodynamics of teicoplanin in elderly critically ill patients with pneumonia for optimal dosages.
Fifteen critically ill patients (9 men) ≥ 60 years received teicoplanin 6 mg/kg for three doses followed by standard maintenance doses (6 mg/kg q24h) with renal dosing adjustment. Serial plasma samples from all patients were analyzed simultaneously by population pharmacokinetic modeling using NONMEM. Probability of target attainment (PTA) was calculated through Monte Carlo simulations for various dosing regimens to achieve adequate systemic exposures.
The median (interquartile range, IQR) age, body mass index, and creatinine clearance (CrCl) was 75 (64-78) years, 22.5 (20.8-25.4) kg/m, and 64 (47-106) mL/min, respectively. The median (IQR) peak and trough concentration was 46.5 (42.7-51.0) and 8.7 (7.2-9.5) mg/L. The population pharmacokinetic model showed slower clearance (CL) and larger peripheral volume of distribution (V2) in patients with reduced CrCl: CL (L/h) = 0.629 × (CrCl/64), V2 (L) = 55.7 × (CrCl/64). Model-based simulations showed PTAs ≥85% only for higher-dose regimens (12 mg/kg) up to an MIC of 0.5 mg/L.
Standard teicoplanin dosages for pneumonia may provide inadequate systemic exposures in elderly critically ill patients. High-dose regimens should be considered as empiric therapy or for less susceptible pathogens.
评估老年重症肺炎患者中替考拉宁的群体药代动力学和药效学，以确定最佳剂量。
15 例（9 名男性）年龄≥60 岁的重症肺炎患者接受替考拉宁 6mg/kg 治疗 3 剂，随后根据肾功能调整剂量，给予标准维持剂量（6mg/kg，q24h）。采用 NONMEM 对所有患者的连续血浆样本进行群体药代动力学建模分析。通过蒙特卡罗模拟计算不同给药方案的达标概率（PTA），以达到足够的全身暴露。
中位（四分位间距，IQR）年龄、体重指数和肌酐清除率（CrCl）分别为 75（64-78）岁、22.5（20.8-25.4）kg/m2和 64（47-106）mL/min。中位（IQR）峰浓度和谷浓度分别为 46.5（42.7-51.0）和 8.7（7.2-9.5）mg/L。群体药代动力学模型显示，CrCl 降低的患者清除率（CL）较慢，外周分布容积（V2）较大：CL（L/h）=0.629×（CrCl/64），V2（L）=55.7×（CrCl/64）。基于模型的模拟结果显示，仅在 MIC 为 0.5mg/L 时，较高剂量方案（12mg/kg）的 PTA≥85%。
肺炎标准替考拉宁剂量可能无法为老年重症患者提供足够的全身暴露。对于敏感性较低的病原体，应考虑使用高剂量方案作为经验性治疗。
