target trough

  • 文章类型: Journal Article
    背景:网络可访问的人群-药代动力学服务-血友病(WAPPS-Hemo)数据可用于研究因子浓缩物的使用,定义为达到3%波谷(WD3T)所需的每周剂量,跨标准和延长半衰期(SHL/EHL)产品。
    目的:提供基线使用数据,包括(i)血浆衍生产品(pdSHL)与重组产品(rSHL)之间的差异,(ii)SHL与EHL,和(iii)年龄和阳性抑制剂史的影响。
    方法:PK概况(n=14,416例患者,0.3-85.2年)和线性混合效应模型用于估计使用量与年龄,控制重要因素,使用95%置信区间在所有年龄之间进行比较,并进行posthoc检验以评估差异.
    结果:在抑制剂病史阳性的患者中,pdSHL的平均使用率明显高于rSHL(PIH;高1.9-2.5倍),对于SHL与EHL(4-10次),并且与年龄显著相关。
    结论:2017年至2023年初的基线使用模式为评估新兴技术在血友病中的影响提供了基准。
    BACKGROUND: Web-Accessible Population-Pharmacokinetic Service-Haemophilia (WAPPS-Hemo) data are available to study factor-concentrate usage, defined as the required weekly dose to achieve a 3% trough (WD3T), across standard and extended half-life (SHL/EHL) products.
    OBJECTIVE: To provide baseline usage data including (i) differences across plasma-derived (pdSHL) versus recombinant (rSHL) products, (ii) SHL versus EHL, and (iii) effect of age and positive inhibitor history.
    METHODS: PK profiles (n = 14,416 patients, 0.3-85.2 years) and linear mixed effects models were used to estimate usage versus age, controlling for significant factors, using 95% confidence intervals to perform comparisons across all ages and posthoc tests to assess the differences.
    RESULTS: Average usage was significantly higher for pdSHL versus rSHL in patients with a positive inhibitor history (PIH; 1.9-2.5 times higher), for SHL versus EHL (4-10 times), and was significantly associated with age.
    CONCLUSIONS: Baseline usage patterns from 2017 to early 2023 provide a benchmark for assessing the impact of emerging technologies in haemophilia.
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  • 文章类型: Journal Article
    Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC24/MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC24 values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC24 A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC24/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC24/MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.
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