Insights into Inhalation Drug Disposition: The Roles of Pulmonary Drug-Metabolizing Enzymes and Transporters

被引:1
|
作者
Dong, Liuhan [1 ]
Zhuang, Xiaomei [1 ]
机构
[1] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China
关键词
pulmonary pharmacokinetics; drug transporters; metabolizing enzymes; inhalation administration; ORGANIC CATION TRANSPORTERS; BRONCHIAL EPITHELIAL-CELLS; IN-VITRO METABOLISM; HUMAN LUNG; P-GLYCOPROTEIN; INHALED DRUG; RECEPTOR OCCUPANCY; RAT LUNG; EXPRESSION; VIVO;
D O I
10.3390/ijms25094671
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The past five decades have witnessed remarkable advancements in the field of inhaled medicines targeting the lungs for respiratory disease treatment. As a non-invasive drug delivery route, inhalation therapy offers numerous benefits to respiratory patients, including rapid and targeted exposure at specific sites, quick onset of action, bypassing first-pass metabolism, and beyond. Understanding the characteristics of pulmonary drug transporters and metabolizing enzymes is crucial for comprehending efficient drug exposure and clearance processes within the lungs. These processes are intricately linked to both local and systemic pharmacokinetics and pharmacodynamics of drugs. This review aims to provide a comprehensive overview of the literature on lung transporters and metabolizing enzymes while exploring their roles in exogenous and endogenous substance disposition. Additionally, we identify and discuss the principal challenges in this area of research, providing a foundation for future investigations aimed at optimizing inhaled drug administration. Moving forward, it is imperative that future research endeavors to focus on refining and validating in vitro and ex vivo models to more accurately mimic the human respiratory system. Such advancements will enhance our understanding of drug processing in different pathological states and facilitate the discovery of novel approaches for investigating lung-specific drug transporters and metabolizing enzymes. This deeper insight will be crucial in developing more effective and targeted therapies for respiratory diseases, ultimately leading to improved patient outcomes.
引用
收藏
页数:24
相关论文
共 50 条
  • [1] Drug-metabolizing enzymes and transporters: Expression in the human prostate and roles in prostate drug disposition
    Obligacion, R
    Murray, M
    Ramzan, I
    JOURNAL OF ANDROLOGY, 2006, 27 (02): : 138 - 150
  • [2] Interplay of Drug-Metabolizing Enzymes and Transporters in Drug Absorption and Disposition
    Shi, Shaojun
    Li, Yunqiao
    CURRENT DRUG METABOLISM, 2014, 15 (10) : 915 - 941
  • [3] Sex and the Kidney Drug-Metabolizing Enzymes and Transporters: Are Preclinical Drug Disposition Data Translatable to Humans?
    Thakur, Aarzoo
    Yue, Guihua
    Ahire, Deepak
    Mettu, Vijaya S.
    Al Maghribi, Abrar
    Ford, Kaitlyn
    Peixoto, Lucia
    Leeder, J. Steven
    Prasad, Bhagwat
    CLINICAL PHARMACOLOGY & THERAPEUTICS, 2024, 116 (01) : 235 - 246
  • [4] The ontogeny of drug-metabolizing enzymes and transporters in the rat
    De Zwart, Loeckie
    Scholten, Martijn
    Monbaliu, Johan
    De Schaepdrijver, Luc
    Bailey, Graham
    Tim, Coogan
    Werner, Coussement
    Van Houdt, Jos
    Geert, Mannens
    DRUG METABOLISM REVIEWS, 2006, 38 : 107 - 108
  • [5] Regulation of drug-metabolizing enzymes and transporters in inflammation
    Aitken, AE
    Richardson, TA
    Morgan, ET
    ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2006, 46 : 123 - 149
  • [6] Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters
    Kim, Vera
    van der Wal, Thijs
    Nishi, Miriam Yumie
    Montenegro, Luciana Ribeiro
    Carrilho, Flair Jose
    Hoshida, Yujin
    Ono, Suzane Kioko
    PHARMACOGENOMICS, 2020, 21 (09) : 575 - 586
  • [7] Changes of Transporters and Drug-metabolizing Enzymes in Nephrotic Syndrome
    Dong, Yaqian
    Gong, Linna
    Lu, Xianyuan
    Ye, Mingguang
    Lin, Yu
    Xie, Shuting
    Zhang, Jiaxing
    Zhou, Fenghua
    Tang, Lan
    Zou, Wei
    Liu, Menghua
    CURRENT DRUG METABOLISM, 2020, 21 (05) : 368 - 378
  • [8] Pharmacogenetic Screening for Polymorphisms in Drug-Metabolizing Enzymes and Drug Transporters in a Dutch Population
    T. M. Bosch
    V. D. Doodeman
    P. H. M. Smits
    I Meijerman
    J. H. M. Schellens
    J. H. Beijnen
    Molecular Diagnosis & Therapy, 2006, 10 : 175 - 185
  • [9] Pharmacogenetic screening for polymorphisms in drug-metabolizing enzymes and drug transporters in a dutch population
    Bosch, T. M.
    Doodeman, V. D.
    SmitS, P. H. M.
    Meijerman, I.
    Schellens, J. H. M.
    Beijnen, J. H.
    MOLECULAR DIAGNOSIS & THERAPY, 2006, 10 (03) : 175 - 185
  • [10] Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer
    Morgan, Edward T.
    Goralski, Kerry B.
    Piquette-Miller, Micheline
    Renton, Kenneth W.
    Robertson, Graham R.
    Chaluvadi, Madhusudana R.
    Charles, Kellie A.
    Clarke, Stephen J.
    Kacevska, Marina
    Liddle, Christopher
    Richardson, Terrilyn A.
    Sharma, Rohini
    Sinal, Christopher J.
    DRUG METABOLISM AND DISPOSITION, 2008, 36 (02) : 205 - 216