Hematological Department, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Pharmacy Department, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Biopharm Drug Dispos. 2021 Nov;42(9):427-434. doi: 10.1002/bdd.2303. Epub 2021 Oct 26.
To explore the clinical application of a population pharmacokinetics (PPK) model of vancomycin in patients with hematological diseases and neutropenia. Patients with hematological diseases and neutropenia were included in the PPK model study. Nonlinear mixed effect modeling approach (NONMEM) was used for model establishment. Monte Carlo simulation was carried out. A total of 74 patients were divided into model group and non-model group for clinical application research. The model group was given the initial dose of 1g q8h, and the non-model group was given 1g q12h as an empiric initial dosage. The follow-up dose adjustments were made according to the concentration results. This two-compartment model showed good stability and accuracy. The first trough concentration (C ) and the compliance rate of the first C were much higher in the model group than that in the non-model group (14.30 ± 4.73 μg/ml and 59.38% vs. 8.02 ± 2.61 μg/ml, 35.71%). Less patients needed dose adjustments and fewer adjustment times in the model group than those in the non-model group (12.50% and 0.13 ± 0.34 times vs. 50.00% and 0.61 ± 0.66 times). This suggested that for those patients who had a Creatinine clearance rate (CLCR) ≥ 90 ml/min/1.73 m , the initial dose of 1g q8h may help to reach the target C (10∼20 μg/ml) quickly. It also helped to reduce the times and number of patients who need dose adjustments. Our PPK model of vancomycin in patients with hematologic diseases and neutropenia can be used to shorten the time to reach the target concentration and reduce the number of dose adjustments.Clinical trial registration: Not applicable (Retrospective study).
探索万古霉素群体药代动力学（PPK）模型在血液病中性粒细胞减少症患者中的临床应用。将血液病中性粒细胞减少症患者纳入 PPK 模型研究。采用非线性混合效应建模方法（NONMEM）建立模型。进行蒙特卡罗模拟。共纳入 74 例患者，分为模型组和非模型组进行临床应用研究。模型组给予首剂 1g，q8h，非模型组给予经验性初始剂量 1g，q12h。根据浓度结果进行后续剂量调整。该两室模型显示出良好的稳定性和准确性。模型组的首次谷浓度（C ）和首次 C 达标率明显高于非模型组（14.30±4.73μg/ml 和 59.38%比 8.02±2.61μg/ml 和 35.71%）。模型组需要调整剂量的患者比例和调整次数均少于非模型组（12.50%和 0.13±0.34 次比 50.00%和 0.61±0.66 次）。这表明对于 CLCR≥90ml/min/1.73m 的患者，首剂 1g，q8h 可能有助于快速达到目标 C （10∼20μg/ml），也有助于减少需要调整剂量的患者比例和次数。本研究建立的血液病中性粒细胞减少症患者万古霉素 PPK 模型可用于缩短达到目标浓度的时间，减少剂量调整次数。临床试验注册号：无（回顾性研究）。
