School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
Kedrion, Laval, Quebec, Canada.
Haemophilia. 2024 Jul;30(4):988-997. doi: 10.1111/hae.15027. Epub 2024 May 2.
Plasminogen deficiency is an ultra rare disease whose patients may develop ligneous lesions if untreated. Prophylactic replacement therapy with plasma derived plasminogen, Ryplazim, is efficient in treating lesions and could benefit from pharmacokinetic (PK) tailoring.
The objectives of this study are to develop, evaluate and integrate into the WAPPS-Hemo platform a Population PK model supporting prophylactic replacement therapy for Plasminogen deficient patients.
Population PK modelling and evaluations followed the same protocol performed for factor VIII and IX concentrates. Limited sampling analysis used dosing and sampling scenarios in accordance with recommended treatment for Ryplazim.
The population PK model, derived from 16 participants included in previous clinical studies, was a 2-compartment model whose variability was best described by fat-free mass. Evaluations showed that the model described well the data and Bayesian forecasting in limited sampling environment led to acceptable precision for PK parameters relevant to plasminogen treatment.
The model was integrated into the WAPPS-Hemo webservice to help individualize prophylactic treatment in plasminogen deficient patients. Prospective PK data to be collected through the WAPPS-Hemo database will be used to better understand plasminogen PK and improve patient care.
纤溶酶原缺乏症是一种极其罕见的疾病，未经治疗的患者可能会出现木质样病变。用血浆来源的纤溶酶原（瑞普青）进行预防性替代治疗可有效治疗病变，并可通过药代动力学（PK）调整获益。
本研究旨在开发、评估并将支持纤溶酶原缺乏症患者预防性替代治疗的群体 PK 模型整合到 WAPPS-Hemo 平台中。
群体 PK 建模和评估遵循与因子 VIII 和 IX 浓缩物相同的方案。有限采样分析根据瑞普青推荐的治疗方案进行了给药和采样方案。
该群体 PK 模型来源于先前临床研究中的 16 名参与者，是一个两室模型，其变异性通过去脂体重得到了最佳描述。评估表明，该模型很好地描述了数据，并且在有限采样环境中的贝叶斯预测可实现与纤溶酶原治疗相关的 PK 参数的可接受精度。
该模型已整合到 WAPPS-Hemo 网络服务中，以帮助个体化纤溶酶原缺乏症患者的预防性治疗。通过 WAPPS-Hemo 数据库收集的前瞻性 PK 数据将用于更好地了解纤溶酶原 PK 并改善患者护理。
