医学
非金属
血友病
加药
血管性血友病因子
血友病A
人口
药代动力学
内科学
儿科
血小板
环境卫生
作者
Noppaket Singkham,Baralee Punyawudho,Ming‐Sun Yu,Shin‐Nan Cheng,Shu‐Huey Chen,Hung Chang,Chih‐Cheng Chen,Chih‐Cheng Hsiao,Jen‐Yin Hou,Yi‐Ping Fang,Hsiang‐Wei Wang,Jia‐Hong Lin,Lennex Hsueh‐Lin Yu,Yeu‐Chin Chen
出处
期刊:Haemophilia
[Wiley]
日期:2022-01-20
卷期号:28 (2): 230-238
被引量:1
摘要
The large interpatient variability in the pharmacokinetic (PK) parameters of recombinant Factor VIII (rFVIII) observed in haemophilia A hinders efficient and cost-beneficial prophylactic regimen initiation. Identification of factors influencing the PK of rFVIII may shed more light on personalised treatment.This study aimed to develop a population PK model in the Taiwanese haemophilia A and evaluate the current national health insurance (NHI) reimbursement guidelines of Taiwan for haemophilia treatment.A population PK analysis was established based on 69 Taiwanese with moderate or severe haemophilia A. A nonlinear mixed-effects modelling (NONMEM® ) was used to estimate PK parameters and their variabilities. A Monte Carlo simulation was performed to evaluate different prophylactic regimens.A two-compartment model with first-order elimination best described the rFVIII data. Weight-based allometric scaling was related to clearance and central volume of distribution. Blood type and baseline von Willebrand factor (VWF) were significant covariates for clearance. For single dose simulations, a time achieving target level (> 1 IU/dL) was associated with increasing rFVIII dose and VWF level. The multiple dose simulations showed that > 96.4% of patients with high VWF level (> 200%) had predicted trough level > 1 IU/dL for all dosing regimens (15-40 IU/kg, two to three times weekly). However, for twice weekly dosing, lower percentage (47.62-62.20%) of patients with blood group O and low VWF level (< 50%) achieved a predicted trough level > 1 IU/dL.The population PK of rFVIII was successfully developed. Dose adjustment based on blood type and VWF level should be considered.
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