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

被引:3
|
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
  • [31] A Review on Drug-Metabolizing Enzymes, Transporters, and Gut Microbiota on Pharmacokinetics in High-Altitude Environment
    Qiu, Fangfang
    Sun, Yuemei
    Li, Wenbin
    Wang, Rong
    CURRENT DRUG METABOLISM, 2025,
  • [32] Effects of atorvastatin metabolites on induction of drug-metabolizing enzymes and membrane transporters through human pregnane X receptor
    Hoffart, E.
    Ghebreghiorghis, L.
    Nussler, A. K.
    Thasler, W. E.
    Weiss, T. S.
    Schwab, M.
    Burk, O.
    BRITISH JOURNAL OF PHARMACOLOGY, 2012, 165 (05) : 1595 - 1608
  • [33] Drug-metabolizing Enzymes and Efflux Transporters in Nasal Epithelium: Influence on the Bioavailability of Intranasally Administered Drugs
    Oliveira, Paula
    Fortuna, Ana
    Alves, Gilberto
    Falcao, Amlcar
    CURRENT DRUG METABOLISM, 2016, 17 (07) : 628 - 647
  • [34] Role of Drug-metabolizing Enzymes in Cancer and Cancer Therapy
    Feng, Siqi
    Li, Anqi
    Zheng, Yi-Chao
    Li, Hong-Min
    CURRENT DRUG METABOLISM, 2020, 21 (01) : 67 - 76
  • [35] Protein abundance of drug transporters and drug-metabolizing enzymes in paired healthy and tumor tissue from colorectal cancer patients
    Steigert, Sebastian
    Brouwers, Joachim
    Vanuytsel, Tim
    Verbandt, Sara
    Tejpar, Sabine
    Oswald, Stefan
    Augustijns, Patrick
    INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2025, 671
  • [36] Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver
    Gaither, Kari A.
    Yue, Guihua
    Singh, Dilip Kumar
    Trudeau, Julia
    Ponraj, Kannapiran
    Davydova, Nadezhda Y.
    Lazarus, Philip
    Davydov, Dmitri R.
    Prasad, Bhagwat
    JOURNAL OF XENOBIOTICS, 2025, 15 (01)
  • [37] EFFECTS OF CYCLAMEN TROCHOPTERANTHUM ON HEPATIC DRUG-METABOLIZING ENZYMES
    Arslan, Sevki
    Ozgun, Ozden
    Celik, Gurbet
    Semiz, Asli
    Dusen, Olcay
    Mammadov, Ramazan
    Sen, Alaattin
    ARCHIVES OF BIOLOGICAL SCIENCES, 2011, 63 (03) : 545 - 555
  • [38] Investigating the Contribution of Drug-Metabolizing Enzymes in Drug-Drug Interactions of Dapivirine and Miconazole
    Valicherla, Guru Raghavendra
    Graebing, Phillip
    Zhang, Junmei
    Zheng, Ruohui
    Nuttall, Jeremy
    Silvera, Peter
    Rohan, Lisa Cencia
    PHARMACEUTICS, 2021, 13 (12)
  • [39] Drug transporters in drug disposition - the year 2022 in review
    Chothe, Paresh P.
    Mitra, Pallabi
    Nakakariya, Masanori
    Ramsden, Diane
    Rotter, Charles J.
    Sandoval, Philip
    Tohyama, Kimio
    DRUG METABOLISM REVIEWS, 2023, 55 (04) : 343 - 370
  • [40] Proteomic Quantification of Changes in Abundance of Drug-Metabolizing Enzymes and Drug Transporters in Human Liver Cirrhosis: Different Methods, Similar Outcomes
    El-Khateeb, Eman
    Al-Majdoub, Zubida M.
    Rostami-Hodjegan, Amin
    Barber, Jill
    Achour, Brahim
    DRUG METABOLISM AND DISPOSITION, 2021, 49 (08) : 610 - 618