Pharmacokinetics of Antibiotics in Patients With Cystic Fibrosis Trated With Elexacaftor/Tezacaftor/Ivacaftor (ETI)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
研究概览
简要总结
Cystic fibrosis (CF) is associated with major pharmacokinetic and pharmacodynamic alterations affecting antibiotic exposure, including changes in absorption, distribution, metabolism, and elimination. Historically, these alterations justified the use of higher antibiotic doses in CF patients in order to achieve therapeutic concentrations and improve pulmonary outcomes.
The advent of highly effective CFTR modulators, particularly the triple combination elexacaftor/tezacaftor/ivacaftor (ETI), has substantially improved pulmonary function, nutritional status, inflammatory burden, and quality of life in patients with CF. ETI therapy also appears to modify respiratory microbiology and reduce the frequency of pulmonary exacerbations.
These clinical and physiological improvements may alter antibiotic pharmacokinetics and pharmacodynamics in patients with CF, potentially making current high-dose antibiotic recommendations less appropriate for some patients. Since repeated exposure to high-dose antibiotics is associated with cumulative toxicities, particularly aminoglycoside-related ototoxicity and nephrotoxicity, reassessment of antibiotic dosing strategies is warranted.
The PKCF study is a multicenter, prospective, observational, non-interventional study designed to characterize the pharmacokinetic profiles of intravenous antibiotics administered during pulmonary exacerbations in adolescents and adults with cystic fibrosis receiving ETI therapy.
详细描述
Patients with cystic fibrosis experience substantial physiological changes that affect the pharmacokinetics of medications, including antibiotics. Altered gastrointestinal absorption, increased volume of distribution, enhanced renal clearance, chronic systemic inflammation, and modified protein binding have historically led to recommendations for increased antibiotic dosing in CF patients.
Additionally, thick airway mucus, biofilm formation, high bacterial inoculum, and chronic airway infection contribute to altered antibiotic pharmacodynamics and reduced antibiotic efficacy.
Highly effective CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), have profoundly changed the clinical course of cystic fibrosis by improving lung function, reducing pulmonary exacerbations, improving nutritional status, and modifying airway microbiology. These changes may normalize or partially normalize antibiotic pharmacokinetics and pharmacodynamics.
However, evidence regarding the impact of ETI therapy on antibiotic pharmacokinetics remains extremely limited. To date, only one retrospective pediatric study has evaluated the effect of CFTR modulators on intravenous tobramycin pharmacokinetics during pulmonary exacerbations.
The PKCF study aims to prospectively evaluate plasma antibiotic concentrations and pharmacokinetic parameters in CF patients receiving ETI during pulmonary exacerbations requiring antibiotic therapy. Antibiotic concentrations will be compared with established PK/PD targets according to current national recommendations.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of cystic fibrosis confirmed by sweat test and/or genetic testing
- •Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least 3 months
- •Age 12 years or older
- •Patient informed and not objecting to participation; for minors, parents/legal guardians informed and not objecting to participation
- •Clinical indication for antibiotic therapy for pulmonary exacerbation or respiratory infection according to treating physician
- •Affiliation to a social security system
排除标准
- •Lung transplantation or heart-lung transplantation
- •Patients under guardianship or curatorship
- •Pregnant or breastfeeding women