Citation: Changzhi Shi, Jelisaveta Ignjatović, Junwei Wang, Yi Guo, Li Zhang, Sandra Cvijić, Dongmei Cun, Mingshi Yang. Evaluating the pharmacokinetics of intrapulmonary administered ciprofloxacin solution for respiratory infections using in vivo and in silico PBPK rat model studies[J]. Chinese Chemical Letters, ;2023, 34(1): 107463. doi: 10.1016/j.cclet.2022.04.061 shu

Evaluating the pharmacokinetics of intrapulmonary administered ciprofloxacin solution for respiratory infections using in vivo and in silico PBPK rat model studies

Changzhi Shi ^a ,
Jelisaveta Ignjatović ^b ,
Junwei Wang ^c ,
Yi Guo ^a ,
Li Zhang ^a ,
Sandra Cvijić ^{b, *,} ,
Dongmei Cun ^a ,
Mingshi Yang ^{a, c, *,}

a.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
b.
Department of Pharmaceutical Technology and Cosmetology, University of Belgrade-Faculty of Pharmacy, Belgrade 11221, Serbia
c.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2100, Denmark

sandra.cvijic@pharmacy.bg.ac.rs

mingshi.yang@sund.ku.dk

Received Date: 27 December 2021
Revised Date: 22 April 2022
Accepted Date: 24 April 2022
Available Online: 29 April 2022

Figures(4)

Respiratory antibiotics have been proven clinically beneficial for the treatment of severe lung infections such as Pseudomonas aeruginosa. Maintaining a high local concentration of inhaled antibiotics for an extended time in the lung is crucial to ensure an adequate antimicrobial efficiency. In this study, we aim to investigate whether an extended exposure of ciprofloxacin (CIP), a model fluoroquinolone drug, in the lung epithelial lining fluid (ELF) could be achieved via a controlled-release formulation strategy. CIP solutions were intratracheally instilled to the rat lungs at 3 different rates, i.e., T0h (fast), T2h (medium), and T4h (slow), to mimic different release profiles of inhaled CIP formulations in the lung. Subsequently, the concentration-time profiles of CIP in the plasma and the lung ELF were obtained, respectively, to determine topical exposure index (ELF-Plasma AUC Ratio, EPR). The in silico PBPK model, validated based on the in vivo data, was used to identify the key factors that influence the disposition of CIP in the plasma and lungs. The medium and slow rates groups exhibited much higher EPR than that fast instillation group. The ELF AUC of the medium and slow instillation groups were about 200 times higher than their plasma AUC. In contrast, the ELF AUC of the fast instillation group was only about 20 times higher than the plasma AUC. The generated whole-body PBPK rat model, validated by comparison with the in vivo data, revealed that drug pulmonary absorption rate was the key factor that determined pulmonary absorption of CIP. This study suggests that controlled CIP release from inhaled formulations may extend the exposure of CIP in the ELF post pulmonary administration. It also demonstrates that combining the proposed intratracheal installation model and in silico PBPK model is a useful approach to identify the key factors that influence the absorption and disposition of inhaled medicine.
- Inhalation antibiotics,
- Ciprofloxacin,
- Controlled release,
- PBPK modeling,
- Lung infections
1. [1]
  Q. Zhou, S.S.Y. Leung, P. Tang, et al., Adv. Drug Deliv. Rev. 85 (2015) 83–99. doi: 10.1016/j.addr.2014.10.022
2. [2]
  J.K. Mukker, R.S.P. Singh, H. Derendorf, Adv. Drug Deliv. Rev. 85 (2015) 57–64. doi: 10.1016/j.addr.2015.03.002
3. [3]
  Y. Guo, H. Bera, C. Shi, et al., Acta Pharm. Sin. B 11 (2021) 2565–2584. doi: 10.1016/j.apsb.2021.05.015
4. [4]
  P.C. Sharma, A. Jain, S. Jain, et al., J. Enzyme Inhib. Med. Chem. 25 (2010) 577–589. doi: 10.3109/14756360903373350
5. [5]
  N. Günday Türeli, A. Torge, J. Juntke, et al., Eur. J. Pharm. Biopharm. 117 (2017) 363–371. doi: 10.1016/j.ejpb.2017.04.032
6. [6]
  X. Zheng, Q. Cao, Q. Cao, et al., Chin. Chem. Lett. 31 (2020) 413–417. doi: 10.1016/j.cclet.2019.07.063
7. [7]
  D. Cipolla, J. Blanchard, I. Gonda, Pharmaceutics 8 (2016) 1–31. doi: 10.3390/pharmaceutics8010001
8. [8]
  E. Gullberg, S. Cao, O.G. Berg, et al., PLoS Pathog. 7 (2011) 1–10.
9. [9]
  E. Wenzler, D.R. Fraidenburg, T. Scardina, et al., Clin. Microbiol. Rev. 29 (2016) 581–632. doi: 10.1128/CMR.00101-15
10. [10]
  T. Karampitsakos, O. Papaioannou, M. Kaponi, et al., Pulm. Pharmacol. Ther. 60 (2020) 101885. doi: 10.1016/j.pupt.2019.101885
11. [11]
  J. Brillault, W.V. De Castro, W. Couet, Antimicrob. Agents Chemother. 54 (2010) 543–545. doi: 10.1128/AAC.00733-09
12. [12]
  H.X. Ong, D. Traini, M. Bebawy, et al., Antimicrob. Agents Chemother. 57 (2013) 2535–2540. doi: 10.1128/AAC.00306-13
13. [13]
  J.E. Hastedt, P. Bäckman, A.R. Clark, et al., AAPS Open 2 (2016) 1–20. doi: 10.1186/s41120-015-0002-x
14. [14]
  A.V.L. Gontijo, J. Brillault, N. Grégoire, et al., Antimicrob. Agents Chemother. 58 (2014) 3942–3949. doi: 10.1128/AAC.02818-14
15. [15]
  J. Brillault, F. Tewes, W. Couet, et al., Eur. J. Pharm. Sci. 97 (2017) 92–98. doi: 10.1016/j.ejps.2016.11.011
16. [16]
  F. Tewes, J. Brillault, B. Lamy, et al., Mol. Pharm. 13 (2016) 100–112. doi: 10.1021/acs.molpharmaceut.5b00543
17. [17]
  B. Lamy, F. Tewes, D.R. Serrano, et al., J. Control. Release 271 (2018) 118–126. doi: 10.1016/j.jconrel.2017.12.021
18. [18]
  S. Yu, S. Wang, P. Zou, et al., Int. J. Pharm. 575 (2020) 118915. doi: 10.1016/j.ijpharm.2019.118915
19. [19]
  G. Chai, H. Park, S. Yu, et al., Int. J. Pharm. 569 (2019) 118616. doi: 10.1016/j.ijpharm.2019.118616
20. [20]
  I. Khatib, D. Khanal, J. Ruan, et al., Int. J. Pharm. 566 (2019) 641–651. doi: 10.1016/j.ijpharm.2019.05.068
21. [21]
  J. Weers, Pulm. Ther. 5 (2019) 127–150. doi: 10.1007/s41030-019-00104-6
22. [22]
  P.J. McShane, J.G. Weers, T.E. Tarara, et al., Pulm. Pharmacol. Ther. 50 (2018) 72–79. doi: 10.1016/j.pupt.2018.03.005
23. [23]
  Q. Wang, L. Ge, L. Wang, et al., Chin. Chem. Lett. 32 (2021) 1071–1076. doi: 10.1016/j.cclet.2020.03.062
24. [24]
  J. Du, J. Guo, D. Kang, et al., Chin. Chem. Lett. 31 (2020) 1695–1708. doi: 10.1016/j.cclet.2020.03.028
25. [25]
  U. Neckel, C. Joukhadar, M. Frossard, et al., Anal. Chim. Acta 463 (2002) 199–206. doi: 10.1016/S0003-2670(02)00429-4
26. [26]
  S. Watabe, Y. Yokoyama, K. Nakazawa, et al., J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 878 (2010) 1555–1561. doi: 10.1016/j.jchromb.2010.04.012
27. [27]
  S. Hansmann, Y. Miyaji, J. Dressman, Eur. J. Pharm. Biopharm. 122 (2018) 186–196. doi: 10.1016/j.ejpb.2017.10.019
28. [28]
  J.F. Schlender, D. Teutonico, K. Coboeken, et al., Clin. Pharmacokinet. 57 (2018) 1613–1634. doi: 10.1007/s40262-018-0661-6
29. [29]
  M.E. Olivera, R.H. Manzo, H.E. Junginger, et al., J. Pharm. Sci. 100 (2011) 22–33. doi: 10.1002/jps.22259
30. [30]
  M. Rodríguez-Ibáñez, G. Sánchez-Castaño, M. Montalar-Montero, et al., Int. J. Pharm. 307 (2006) 33–41. doi: 10.1016/j.ijpharm.2005.09.014
31. [31]
  M.H. Park, S.H. Shin, J.J. Byeon, et al., Korean J. Physiol. Pharmacol. 21 (2017) 107–115. doi: 10.4196/kjpp.2017.21.1.107
32. [32]
  S. Li, Y. Yu, X. Bian, et al., Arch. Toxicol. 95 (2021) 1683–1701. doi: 10.1007/s00204-021-03023-1
33. [33]
  B. Nouaille-Degorce, C. Veau, S. Dautrey, et al., Antimicrob. Agents Chemother. 42 (1998) 289–292.
1. [1]
  Fei-Yan Gao , Yan Wu , Ling Yang , Zhong-Yi Ma , Yi Chen , Xiao-Man Mao , Xu-Fei Bian , Pei Tang , Chong Li . Orally delivered berberine derivatives for dual therapy in diabetic complications with MRSA infections. Chinese Chemical Letters, 2025, 36(4): 109917-. doi: 10.1016/j.cclet.2024.109917
2. [2]
  Hui Wang , Haodong Ji , Dandan Zhang , Xudong Yang , Hanchun Chen , Chunqian Jiang , Weiliang Sun , Jun Duan , Wen Liu . Solar-light-driven photocatalytic degradation and detoxification of ciprofloxacin using sodium niobate nanocubes decorated g-C₃N₄ with built-in electric field. Chinese Chemical Letters, 2025, 36(5): 110200-. doi: 10.1016/j.cclet.2024.110200
3. [3]
  Jiaxu Wang , Jinxie Zhang , Xiuping Wang , Jingying Wang , Lina Chen , Jiahui Cao , Wei Cao , Siyu Liang , Ping Luan , Ke Zheng , Xiao-Kun Ouyang , Li Gao , Xiaowen Ou , Fan Zhang , Meitong Ou , Lin Mei . CaCO₃-coated hollow mesoporous silica nanoparticles for pH-responsive fungicides release. Chinese Chemical Letters, 2024, 35(12): 109697-. doi: 10.1016/j.cclet.2024.109697
4. [4]
  Mengwei Ye , Qingqing Xu , Huanhuan Jian , Yiduo Ding , Wenpeng Zhao , Chenxiao Wang , Junya Lu , Shuaipeng Feng , Siling Wang , Qinfu Zhao . Recent trends of biodegradable mesoporous silica based nanoplatforms for enhanced tumor theranostics. Chinese Chemical Letters, 2025, 36(6): 110221-. doi: 10.1016/j.cclet.2024.110221
5. [5]
  Shifang Song , Chenyu Wu , Li Zhang , Dezhi Yang , Yang Lu , Zhengzheng Zhou . Unpacking phase transitions in multi-component drug systems: A case study. Chinese Chemical Letters, 2025, 36(7): 110911-. doi: 10.1016/j.cclet.2025.110911
6. [6]
  Wenping Dong , Mo Ma , Jingkang Li , Lanlan Xu , Dejiang Gao , Pinyi Ma , Daqian Song . Near-infrared fluorescent probe with large Stokes shift and long emission wavelength for rapid diagnosis of lung cancer via aerosol inhalation delivery. Chinese Chemical Letters, 2025, 36(5): 110147-. doi: 10.1016/j.cclet.2024.110147
7. [7]
  Haoyu Luo , Jinsong Chen , Mengfei Luo , Hui Ma , Shengyan Pu . Heterogeneous Fenton catalytic degradation of nitrobenzene by controlled-release nano calcium peroxide. Chinese Chemical Letters, 2025, 36(6): 110367-. doi: 10.1016/j.cclet.2024.110367
8. [8]
  Dongdong YANG , Jianhua XUE , Yuanyu YANG , Meixia WU , Yujia BAI , Zongxuan WANG , Qi MA . Design and synthesis of two coordination polymers for the rapid detection of ciprofloxacin based on triphenylpolycarboxylic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2466-2474. doi: 10.11862/CJIC.20240266
9. [9]
  Tong Zhang , Chao Sun , Shubin Yang , Zimin Cai , Sifeng Zhu , Wendian Liu , Yun Luan , Cheng Wang . Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis. Chinese Chemical Letters, 2024, 35(8): 109248-. doi: 10.1016/j.cclet.2023.109248
10. [10]
  Zhipeng Li , Qincong Feng , Jianliang Shen . A β-lactamase-activatable photosensitizer for the treatment of resistant bacterial infections. Chinese Chemical Letters, 2024, 35(11): 109602-. doi: 10.1016/j.cclet.2024.109602
11. [11]
  Kexin Yuan , Yulei Liu , Haoran Feng , Yi Liu , Jun Cheng , Beiyang Luo , Qinglian Wu , Xinyu Zhang , Ying Wang , Xian Bao , Wanqian Guo , Jun Ma . Unlocking the potential of thin-film composite reverse osmosis membrane performance: Insights from mass transfer modeling. Chinese Chemical Letters, 2024, 35(5): 109022-. doi: 10.1016/j.cclet.2023.109022
12. [12]
  Zhuan Chen , Bo Yang , Jun Li , Kun Du , Jiangchen Fu , Xiao Wu , Jiazhen Cao , Mingyang Xing . Environmentally safe storage and sustained release of hydrogen peroxide utilizing commercial hydrogel. Chinese Chemical Letters, 2025, 36(6): 110320-. doi: 10.1016/j.cclet.2024.110320
13. [13]
  Yang Liu , Leilei Zhang , Kaixuan Liu , Ling-Ling Wu , Hai-Yu Hu . Penicillin G acylase-responsive near-infrared fluorescent probe: Unravelling biofilm regulation and combating bacterial infections. Chinese Chemical Letters, 2024, 35(11): 109759-. doi: 10.1016/j.cclet.2024.109759
14. [14]
  Yuxin Li , Chengbin Liu , Qiuju Li , Shun Mao . Fluorescence analysis of antibiotics and antibiotic-resistance genes in the environment: A mini review. Chinese Chemical Letters, 2024, 35(10): 109541-. doi: 10.1016/j.cclet.2024.109541
15. [15]
  Hao Wang , Meng-Qi Pan , Ya-Fei Wang , Chao Chen , Jian Xu , Yuan-Yuan Gao , Chuan-Song Qi , Wei Li , Xian-He Bu . Post-synthetic modifications of MOFs by different bolt ligands for controllable release of cargoes. Chinese Chemical Letters, 2024, 35(10): 109581-. doi: 10.1016/j.cclet.2024.109581
16. [16]
  Zheyi Li , Xiaoyang Liang , Zitong Qiu , Zimeng Liu , Siyu Wang , Yue Zhou , Nan Li . Ion-interferential cell cycle arrest for melanoma treatment based on magnetocaloric bimetallic-ion sustained release hydrogel. Chinese Chemical Letters, 2024, 35(11): 109592-. doi: 10.1016/j.cclet.2024.109592
17. [17]
  Yue Ren , Kang Li , Yi-Zi Wang , Shao-Peng Zhao , Shu-Min Pan , Haojie Fu , Mengfan Jing , Yaming Wang , Fengyuan Yang , Chuntai Liu . Swelling and erosion assisted sustained release of tea polyphenol from antibacterial ultrahigh molecular weight polyethylene for joint replacement. Chinese Chemical Letters, 2025, 36(2): 110468-. doi: 10.1016/j.cclet.2024.110468
18. [18]
  Zhixiao Xiong , Shanni Qiu , Yuyu Wang , Houna Duan , Yi Xiao , Yufang Xu , Weiping Zhu , Xuhong Qian . Photocalibrated NO release from the zinc ion fluorescent probe based on naphthalimide and its application in living cells. Chinese Chemical Letters, 2025, 36(4): 110002-. doi: 10.1016/j.cclet.2024.110002
19. [19]
  Yuhan Zhang , Xiao-Lin Zhang , Han Ding , Yuan Xu , Xue-Wei Liu . Catalytic ring-strain release toward a facial and efficient synthesis of versatile C-glycosides. Chinese Chemical Letters, 2025, 36(7): 110560-. doi: 10.1016/j.cclet.2024.110560
20. [20]
  Xiaohong Wen , Mei Yang , Lie Li , Mingmin Huang , Wei Cui , Suping Li , Haiyan Chen , Chen Li , Qiuping Guo . Enzymatically controlled DNA tetrahedron nanoprobes for specific imaging of ATP in tumor. Chinese Chemical Letters, 2024, 35(8): 109291-. doi: 10.1016/j.cclet.2023.109291

Get Citation

PDF

XML

Metrics

PDF Downloads(10)
Abstract views(849)
HTML views(77)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142