Awaness Ayda, Elkeeb Rania, Afshari Sepehr, Atef Eman
Pharmacy School, West Coast University, Los Angeles, CA 90004, USA.
Medicines (Basel). 2024 Dec 31;12(1):1. doi: 10.3390/medicines12010001.
Cystic fibrosis (CF) is a rare genetic disorder commonly affecting multiple organs such as the lungs, pancreas, liver, kidney, and intestine. Our search focuses on the pathophysiological changes that affect the drugs' absorption, distribution, metabolism, and excretion (ADME). This review aims to identify the ADME data that compares the pharmacokinetics (PK) of different drugs in CF and healthy subjects. The published data highlight multiple factors that affect absorption, such as the bile salt precipitation and the gastrointestinal pH. Changes in CF patients' protein binding and body composition affected the drug distribution. The paper also discusses the factors affecting metabolism and renal elimination, such as drug-protein binding and metabolizing enzyme capacity. The majority of CF patients are on multidrug therapy, which increases the risk of drug-drug interactions (DDI). This is particularly true for those receiving the newly developed transmembrane conductance regulator (CFTR), as they are at a higher risk for CYP-related DDI. Our research highlights the importance of meticulously evaluating PK variations and DDIs in drug development and the therapeutic management of CF patients.
囊性纤维化（CF）是一种罕见的遗传性疾病，通常会影响多个器官，如肺、胰腺、肝脏、肾脏和肠道。我们的研究重点是影响药物吸收、分布、代谢和排泄（ADME）的病理生理变化。本综述旨在确定比较CF患者和健康受试者中不同药物药代动力学（PK）的ADME数据。已发表的数据突出了多种影响吸收的因素，如胆盐沉淀和胃肠道pH值。CF患者蛋白质结合和身体组成的变化影响了药物分布。本文还讨论了影响代谢和肾脏排泄的因素，如药物与蛋白质的结合以及代谢酶的能力。大多数CF患者接受多种药物治疗，这增加了药物相互作用（DDI）的风险。对于那些接受新开发的跨膜电导调节剂（CFTR）治疗的患者来说尤其如此，因为他们发生与细胞色素P450（CYP）相关的DDI的风险更高。我们的研究强调了在CF患者的药物开发和治疗管理中精心评估PK变化和DDI的重要性。
