击中目标:在患有囊性纤维化的儿科患者中以模型为基础的托布拉米辛精确剂量
Jake M Brockmeyer1, Laura Bio1, Carlos Milla2
1Department of Pharmacy, Lucile Packard Children's Hospital Stanford, Palo Alto, CA 94304, USA.
Pharmaceuticals (Basel, Switzerland)
|January 28, 2026
概括
基于模型的精确剂量 (MIPD) 改善了小儿囊性纤维化 (CF) 患者的托布拉米辛治疗. 这种方法优化了药物水平,减少了监测需求和剂量调整,同时保持了安全性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 儿科医学 儿科医学
- 传染性疾病 传染性疾病
背景情况:
- 托布拉米辛对于治疗儿科囊性纤维化 (CF) 患者的肺部恶化至关重要.
- 可变的药理动力学和狭窄的治疗指数需要对托布拉米进行治疗药物监测 (TDM).
- 基于模型的精确剂量 (MIPD) 提供了一种使用人口PK模型和贝叶斯预测来个性化药物剂量的方法.
研究的目的:
- 评估MIPD倡议对小儿CF患者每天一次托布拉米辛剂量的有效性.
- 为了比较TDM实践和MIPD实施前后的结果.
- 评估MIPD对实现目标托布拉米辛暴露和患者安全的影响.
主要方法:
- 一项比较研究分析了21岁以下CF患者的托布拉米辛治疗疗程.
- 在MIPD前 (2016-2018) 期间,用于TDM的传统日志线性AUC计算.
- 在MIPD后期 (2019-2025) 使用商业MIPD软件平台集成到EHR中.
主要成果:
- 在MIPD后的实施显示,在TDM1,TDM2和TDM3.3时,目标24小时曲线下面积 (AUC24) 的实现明显更高.
- 在MIPD期间,在治疗的前7天内,需要较少的TDM样本 (4.2比7.1) 和剂量调整 (0.7比1.8).
- 急性损伤 (AKI) 的发生率仍然很低,在MIPD前和MIPD后的时期之间可以比较.
结论:
- 在儿童CF患者中实施MIPD对托布拉米辛的倡议可以提高治疗AUC24目标的早期实现.
- MIPD显著降低了TDM负担和所需剂量调整的数量.
- MIPD方法有效地优化了托布拉米辛治疗,同时保持了低毒性风险.
相关概念视频
Cystic Fibrosis: Pathogenesis
868
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
868
Cystic Fibrosis: Management
520
Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic...
Sinus disease and chronic...
520
Pharmacokinetics in Pediatric Patients: Drug Excretion
225
In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
225
Drug Dosing: Geriatric Patients
232
Elderly individuals encompass a diverse population with varying degrees of age-related physiological changes. Defining the elderly presents challenges, as the geriatric population is often arbitrarily categorized as individuals older than 65. However, many individuals in this group lead active and healthy lives, with an increasing number surpassing 85 years and falling into the older elderly category. Physiological changes associated with aging impact performance capacity and homeostatic...
232
Drug Dosing: Obese Patients
254
In the United States, obesity is a prominent concern. It is linked to heightened mortality rates due to increased occurrences of conditions such as hypertension, atherosclerosis, coronary artery disease, and diabetes compared to nonobese individuals. A patient is classified as obese if their actual body weight surpasses the ideal or desirable body weight by 20%, based on Metropolitan Life Insurance Company data. Ideal body weights consider average weights and heights for males and females...
254
Pharmacokinetics in Pediatric Patients: Drug Distribution
285
Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight,...
285


