PDF(Pubmed)
Abstract：
Background: Due to the heterogeneity of critically ill patients, the pharmacokinetics of tigecycline are unclear, and the optimal dosing strategy is controversial. Methods: A single-center prospective clinical study that included critically ill patients who received tigecycline was performed. Blood samples were intensively sampled (eight samples each), and plasma drug concentrations were determined. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis and visual predictive checks. Monte Carlo simulation was conducted to optimize the dosage regimen. Results: Overall, 751 observations from 98 patients were included. The final PPK model was a two-compartment model incorporating covariates of creatinine clearance on clearance (CL), body weight on both central and peripheral volumes of distribution (V1 and V2), γ-glutamyl transferase and total bilirubin on intercompartment clearance (Q), and albumin on V2. The typical values of CL, Q, V1 and V2 were 3.09 L/h, 39.7 L/h, 32.1 L and 113 L, respectively. A dosage regimen of 50 mg/12 h was suitable for complicated intra-abdominal infections, but 100 mg/12 h was needed for community-acquired pneumonia, skin and skin structure infections and infections caused by less-susceptive bacteria. Conclusion: The Tigecycline PPK model was successfully developed and validated. Individualized dosing of tigecycline could be beneficial for critically ill patients.
摘要：
背景:由于危重病人的异质性,替加环素的药代动力学尚不清楚，最佳给药策略是有争议的。方法：进行单中心前瞻性临床研究，包括接受替加环素治疗的危重患者。对血液样本进行了密集采样（每个样本八个），并测定血浆药物浓度。建立了群体药代动力学（PPK）模型，并通过拟合优度图进行了评估，引导分析和视觉预测检查。进行蒙特卡罗模拟以优化给药方案。结果：总体而言，包括来自98例患者的751个观察结果。最终的PPK模型是包含肌酐清除率（CL）协变量的两室模型，中心和外周分布体积上的体重（V1和V2），γ-谷氨酰转移酶和总胆红素对室间清除（Q），和白蛋白在V2上。CL的典型值，Q,V1和V2为3.09L/h,39.7L/h,32.1升和113升，分别。50mg/12h的给药方案适用于复杂的腹腔内感染，但是社区获得性肺炎需要100毫克/12小时，由敏感性较低的细菌引起的皮肤和皮肤结构感染。结论:成功建立并验证了替加环素PPK模型。替加环素的个体化给药可能对危重患者有益。
