Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Reddel, H.K.; Bacharier, L.B.; Bateman, E.D.; Brightling, C.E.; Brusselle, G.G.; Buhl, R.; Cruz, A.A.; Duijts, L.; Drazen, J.M.; FitzGerald, J.M.; et al. Global Initiative for Asthma Strategy 2021. Executive Summary and Rationale for Key Changes. Arch. Bronconeumol. 2022, 58, 35–51. [Google Scholar] [CrossRef] [PubMed]
- Plaza, V.; Alobid, I.; Alvarez, C.; Blanco, M.; Ferreira, J.; García, G.; Gómez-Outes, A.; Gómez, F.; Hidalgo, A.; Korta, J.; et al. Spanish Asthma Management Guidelines (GEMA) VERSION 5.1. Highlights and Controversies. Arch. Bronconeumol. 2022, 58, 150–158. [Google Scholar] [CrossRef] [PubMed]
- Miravitlles, M.; Calle, M.; Molina, J.; Almagro, P.; Gomez, J.T.; Trigueros, J.A.; Cosio, B.G.; Casanova, C.; Lopez-Campos, J.L.; Riesco, J.A.; et al. Spanish COPD Guidelines (GesEPOC) 2021: Updated Pharmacological treatment of stable COPD. Arch. Bronconeumol. 2022, 58, 69–81. [Google Scholar] [CrossRef] [PubMed]
- Agusti, A.; Celli, B.R.; Criner, G.J.; Halpin, D.; Anzueto, A.; Barnes, P.; Bourbeau, J.; Han, M.K.; Martinez, F.J.; Montes de Oca, M.; et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Arch. Bronconeumol. 2023, 59, 232–248. [Google Scholar] [CrossRef]
- Dekhuijzen, P.N.R.; Levy, M.L.; Corrigan, C.J.; Hadfield, R.M.; Roche, N.; Usmani, O.S.; Barnes, P.J.; Scullion, J.E.; Lavorini, F.; Corbetta, L.; et al. Is Inhaler Technique Adequately Assessed and Reported in Clinical Trials of Asthma and Chronic Obstructive Pulmonary Disease Therapy? A Systematic Review and Suggested Best Practice Checklist. J. Allergy Clin. Immunol. Pract. 2022, 10, 1813–1824.e1. [Google Scholar] [CrossRef]
- Molina París, J. Inhalation Devices and Climatic Change. Arch. Bronconeumol. 2022, 58, 287. [Google Scholar] [CrossRef]
- Alonso-Pérez, T.; García-Castillo, E.; López-Campos, J.L. Escalation and de-escalation of therapy in chronic obstructive pulmonary disease. Is the inhaler important? Arch. Bronconeumol. 2021, 57, 604–605. [Google Scholar] [CrossRef]
- Cosío, B.G.; Shafiek, H.; Martínez-García, M. Is it Time to Readjust the Doses of Inhaled Corticosteroids in COPD? Arch. Bronconeumol. 2022, 58, 593–594. [Google Scholar] [CrossRef]
- Clarà, P.C.; Jerez, F.R.; Ramírez, J.B.; González, C.M. Deposition and Clinical Impact of Inhaled Particles in the Lung. Arch. Bronconeumol. 2023, 59, 377–382. [Google Scholar] [CrossRef]
- Seale, J.P.; Harrison, L.I. Effect of changing the fine particle mass of inhaled beclomethasone dipropionate on intrapulmonary deposition and pharmacokinetics. Respir. Med. 1998, 92 (Suppl. A), 9–15. [Google Scholar] [CrossRef][Green Version]
- Hargreaves, C.; Budgen, N.; Whiting, A.; Lachacz, K.; Sommerville, M.; Archbell, J.; Joshi, V. S60—A new medical propellant HFO-1234ze(E): Reducing the environmental impact of inhaled medicines. Thorax 2022, 77, A38–A39. [Google Scholar] [CrossRef]
- D’Urzo, A.; Kerwin, E.; Overend, T.; D’Andrea, P.; Chen, H.; Goyal, P. Once daily glycopyrronium for the treatment of COPD: Pooled analysis of the GLOW1 and GLOW2 studies. Curr. Med. Res. Opin. 2014, 30, 493–508. [Google Scholar] [CrossRef] [PubMed]
- LaForce, C.; Feldman, G.; Spangenthal, S.; Eckert, J.H.; Henley, M.; Patalano, F.; D’Andrea, P. Efficacy and safety of twice-daily glycopyrrolate in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation: The GEM1 study. Int. J. Chron. Obstr. Pulm. Dis. 2016, 11, 1233–1243. [Google Scholar] [CrossRef][Green Version]
- Kerwin, E.; Siler, T.M.; Korenblat, P.; White, A.; Eckert, J.H.; Henley, M.; Patalano, F.; D’Andrea, P. Efficacy and Safety of Twice-Daily Glycopyrrolate Versus Placebo in Patients with COPD: The GEM2 Study. Chronic Obstr. Pulm. Dis. 2016, 3, 549–559. [Google Scholar] [CrossRef][Green Version]
- Fan, Z.; Zhou, B.; Liu, Y.; Sun, W.; Fang, Y.; Lu, H.; Chen, D.; Lu, K.; Wu, X.; Xiao, T.; et al. Optimization and Application of an Efficient and Stable Inhalation Exposure System for Rodents. AAPS PharmSciTech 2022, 23, 50. [Google Scholar] [CrossRef] [PubMed]
- Kumon, M.; Machida, S.; Suzuki, M.; Kusai, A.; Yonemochi, E.; Terada, K. Application and mechanism of inhalation profile improvement of DPI formulations by mechanofusion with magnesium stearate. Chem. Pharm. Bull. 2008, 56, 617–625. [Google Scholar] [CrossRef]
- Gillespie, M.; Song, S.; Steinfeld, J. Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus a prevailing dry powder inhaler and a metered-dose inhaler. Allergy Asthma Proc. 2015, 36, 365–371. [Google Scholar] [CrossRef]
- Miller, D.S.; Yiu, G.; Hellriegel, E.T.; Steinfeld, J. Dose-ranging study of salmeterol using a novel fluticasone propionate/salmeterol multidose dry powder inhaler in patients with persistent asthma. Allergy Asthma Proc. 2016, 37, 291–301. [Google Scholar] [CrossRef]
- Kerwin, E.M.; Gillespie, M.; Song, S.; Steinfeld, J. Randomized, dose-ranging study of a fluticasone propionate multidose dry powder inhaler in adolescents and adults with uncontrolled asthma not previously treated with inhaled corticosteroids. J. Asthma 2017, 54, 89–98. [Google Scholar] [CrossRef]
- Buhl, R.; Tanase, A.M.; Hosoe, M.; Cao, W.; Demin, I.; Bartels, C.; Jauernig, J.; Ziegler, D.; Patalano, F.; Hederer, B.; et al. A randomized, double-blind study to compare the efficacy and safety of two doses of mometasone furoate delivered via Breezhaler® or Twisthaler® in patients with asthma. Pulm. Pharmacol. Ther. 2020, 62, 101919. [Google Scholar] [CrossRef]
- Buhl, R.; Nikolaev, I.; Tillmann, H.C.; Vaidya, S.; Bartels, C.; Jain, M.; Jauernig, J.; Kerstjens, H.A.M. Dose bridging data for mometasone furoate in once-daily fixed-dose inhaled combinations of mometasone furoate/indacaterol and mometasone furoate/ indacaterol/glycopyrronium in patients with asthma. Pulm. Pharmacol. Ther. 2021, 70, 102068. [Google Scholar] [CrossRef] [PubMed]
- Wei, X.; Hindle, M.; Kaviratna, A.; Huynh, B.K.; Delvadia, R.R.; Sandell, D.; Byron, P.R. In Vitro Tests for Aerosol Deposition. VI: Realistic Testing with Different Mouth-Throat Models and In Vitro-In Vivo Correlations for a Dry Powder Inhaler, Metered Dose Inhaler, and Soft Mist Inhaler. J. Aerosol Med. Pulm. Drug Deliv. 2018, 31, 358–371. [Google Scholar] [CrossRef]
- Van der Kolk, H.; Zanen, P.; Tushuizen, E.; Gusdorf, C.F. The effect of inhalation flow on the performance of a dry powder inhalation system. Eur. J. Drug Metab. Pharmacokinet. 1991, 3, 415–418. [Google Scholar]
- Pavkov, R.; Mueller, S.; Fiebich, K.; Singh, D.; Stowasser, F.; Pignatelli, G.; Walter, B.; Ziegler, D.; Dalvi, M.; Dederichs, J.; et al. Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol. Curr. Med. Res. Opin. 2010, 26, 2527–2533. [Google Scholar] [CrossRef]
- De la Rosa Carrillo, D.; Martínez-García, M.; Barreiro, E.; Tabernero Huguet, E.; Costa Sola, R.; García-Clemente, M.M.; Celorrio Jiménez, N.; Rodríguez Pons, L.; Calero Acuña, C.; Rodríguez Hermosa, J.L.; et al. Effectiveness and Safety of Inhaled Antibiotics in Patients with Chronic Obstructive Pulmonary Disease. A Multicentre Observational Study. Arch. Bronconeumol. 2022, 58, 11–21. [Google Scholar] [CrossRef] [PubMed]
- Bianchera, A.; Alomari, E.; Michielon, A.; Bazzoli, G.; Ronda, N.; Pighini, G.; Zanotti, I.; Giorgio, C.; Mozzarelli, A.; Bettini, R.; et al. Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept. Pharmaceutics 2022, 14, 2754. [Google Scholar] [CrossRef]
- Navas-Bueno, B.; Casas-Maldonado, F.; Padilla-Galo, A.; González-Moya-Mondelo, E.; Arenas-Gordillo, M.; Bioque-Rivera, J.C.; Jimeno-Galván, R.; Cano-Gómez, M.S.; López-Campos, J.L.; Merlos-Navarro, S.; et al. High Adherence, Microbiological Control and Reduced Exacerbations in Patients with Non-Cystic Fibrosis Bronchiectasis Treated with Nebulised Colistin: A Prospective Observational Study. Arch. Bronconeumol. 2022, 58, 834–836. [Google Scholar] [CrossRef]
(a) Salmeterol | ||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||
– | Salmeterol xinafoate | – | Salmeterol xinafoate | |
Serevent MDI 25 | – | 25 | – | NA |
Serevent Accuhaler 50 | – | 50 | – | NA |
(b) Tiotropium-olodaterol | ||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||
Tiotropium bromide monohydrate | Olodaterol hydrochloride | Tiotropium bromide monohydrate | Olodaterol hydrochloride | |
Spiriva Handihaler 18 | 22.5 (18) | – | ? (10) | – |
Braltus Zonda 10 | 16 (13) | – | ? (10) | – |
Tavulus Inhalator 18 | 21.7 (18) | – | ? (10) | – |
Spiriva Respimat 2.5 | NA | – | 3.124 (2.5) | – |
Striverdi Respimat 2.5 | – | NA | – | 2.5 |
Spiolto Respimat 2.5/2.5 | NA | NA | 2.5 | 2.5 |
(c) Glycopyrronium-indacaterol | ||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||
Glycopyrronium bromide | Indacaterol maleate | Glycopyrronium bromide | Indacaterol maleate | |
Onbrez Breezhaler 150 | – | ? (150) | – | ? (120) |
Onbrez Breezhaler 300 | – | ? (300) | – | ? (240) |
Seebri Breezhaler 44 | 63 (50) | – | 55 (44) | – |
Ultibro Breezhaler 85/43 | 63 (50) | 143 (110) | 54 (43) | 110 (85) |
(d) Aclidinium-formoterol | ||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||
Aclidinium bromide | Formoterol fumarate dihydrate | Aclidinium bromide | Formoterol fumarate dihydrate | |
Foradil Areolizer 12 | – | 12 | – | ? |
Foradil Neo MDI 12 | – | 12 | – | 10.1 |
Formatris Novolizer 12 | – | 12 | – | 10.2 (8.36) |
Formatris Novolizer 6 | – | 6 | 5.1 (4.18) | |
Oxis Turbuhaler 9 | – | 12 | – | 9 |
Oxis Turbuhaler 4.5 | – | 6 | – | 4.5 |
Eklira Genuair 322 | 400 (343) | – | 375 (322) | – |
Duaklir Genuair 340/12 | 400 (343) | 12 | 396 (340) | 11.8 |
(e) Umeclidinium-vilanterol | ||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||
Umeclidinium bromide | Vilanterol trifenatate | Umeclidinium bromide | Vilanterol trifenatate | |
Incruse Ellipta 55 | 74.2 (62.5) | – | 65 (55) | – |
Anoro Ellipta 55/22 | 74.2 (62.5) | 25 | 65 (55) | 22 |
(a) Beclomethasone | ||||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||||
Beclomethasone dipropionate | – | – | Beclomethasone dipropionate | – | – | |
Beclo-Asma MDI 50 | 50 | – | – | NA | – | – |
Beclo-Asma MDI 100 | 100 | – | – | NA | – | – |
Becloforte MDI 250 | 250 | – | – | NA | – | – |
Becotide MDI 50 | 50 | – | – | NA | – | – |
Soprobec MDI 50 | 50 | – | – | NA | – | – |
Soprobec MDI 100 | 100 | – | – | NA | – | – |
Soprobec MDI 200 | 200 | – | – | NA | – | – |
Soprobec MDI 250 | 250 | – | – | NA | – | – |
(b) Beclomethasone extra fine | ||||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||||
Beclomethasone dipropionate | Formoterol fumarate dihydrate | Glycopyrronium bromide | Beclomethasone dipropionate | Formoterol fumarate dihydrate | Glycopyrronium bromide | |
Foster MDI 100/6 | 100 | 6 | – | 84.6 | 5.0 | – |
Foster MDI 200/6 | 200 | 6 | – | 177.7 | 5.1 | – |
Foster Nexthaler 100/6 | 100 | 6 | – | 81.9 | 5.0 | – |
Foster Nexthaler 200/6 | 200 | 6 | – | 158.8 | 4.9 | – |
Trimbow MDI 87/5/9 | 100 | 6 | 12.5 (10) | 87 | 5.0 | 11 (9) |
Trimbow MDI 172/5/9 | 200 | 6 | 12.5 (10) | 172 | 5.0 | 11 (9) |
Trimbow Nexthaler 88/5/9 | 100 | 6 | 12.5 (10) | 88 | 5.0 | 11 (9) |
(c) Budesonide | ||||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||||
Budesonide | Formoterol fumarate dihydrate | Glycopyrronium bromide | Budesonide | Formoterol fumarate dihydrate | Glycopyrronium bromide | |
Pulmicort Turbuhaler 100 | 100 | – | – | ? | – | – |
Pulmicort Turbuhaler 200 | 200 | – | – | ? | – | – |
Pulmicort Turbuhaler 400 | 400 | – | – | ? | – | – |
Budesonida Easyhaler 100 | 100 | – | – | 100 | – | – |
Budesonida Easyhaler 200 | 200 | – | – | 200 | – | – |
Budesonida Easyhaler 400 | 400 | – | – | 400 | – | – |
Miflonide Breezhaler 200 | 230 | – | – | 200 | – | – |
Miflonide Breezhaler 400 | 460 | – | – | 400 | – | – |
Symbicort Turbuhaler 80/4.5 | 100 | 6 | – | 80 | 4.5 | – |
Symbicort Turbuhaler 160/4.5 | 200 | 6 | – | 160 | 4.5 | – |
Symbicort Turbuhaler 320/9 | 400 | 12 | – | 320 | 9 | – |
Symbicort MDI 80/2.25 | 100 | 3 | – | 80 | 2.25 | – |
Symbicort MDI 160/4.5 | 200 | 6 | – | 160 | 4.5 | – |
Symbicort MDI 320/9 | 400 | 12 | – | 320 | 9 | – |
Duoresp Spiromax 160/4.5 | 200 | 6 | – | 160 | 4.5 | – |
Duoresp Spiromax 320/9 | 400 | 12 | – | 320 | 9 | – |
Bufomix Easyhaler 160/4.5 | 160 | 4.5 | – | 160 | 4.5 | – |
Bufomix Easyhaler 320/9 | 320 | 9 | – | 320 | 9 | – |
Trixeo Aerosphere 5/7.2/160 | 170 | 5.3 | 9.6 (7.7) | 160 | 5 | 9 (7.2) |
(d) Ciclesonide | ||||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||||
Ciclesonide | – | – | Ciclesonide | – | – | |
Alvesco MDI 160 | 200 | – | – | 160 | – | – |
(e) Fluticasone propionate + salmeterol | ||||||
Product name as first marketed in Spain * | Metered dose † | Delivered dose † | ||||
Fluticasone propionate | Salmeterol xinafoate | – | Fluticasone propionate | Salmeterol xinafoate | – | |
Flixotide MDI 50 | 50 | – | – | NA | – | – |
Flixotide MDI 125 | 125 | – | – | NA | – | – |
Flixotide MDI 250 | 250 | – | – | NA | – | – |
Flixotide Accuhaler 100 | 100 | – | – | NA | – | – |
Flixotide Accuhaler 500 | 500 | – | – | NA | – | – |
Seretide MDI 25/50 | 50 | 25 | – | 44 | 21 | – |
Seretide MDI 25/125 | 125 | 25 | – | 110 | 21 | – |
Seretide MDI 25/250 | 250 | 25 | – | 220 | 21 | – |
Seretide Accuhaler 50/100 | 100 | 50 | – | 92 | 47 | – |
Seretide Accuhaler 50/250 | 250 | 50 | – | 231 | 47 | – |
Seretide Accuhaler 50/500 | 500 | 50 | – | 460 | 47 | – |
Flusamix Easyhaler 50/500 | 500 | 50 | – | 476 | 48 | – |
Aerivio Spiromax 50/500 | 500 | 50 | – | 465 | 45 | – |
Airflusal Forspiro 50/250 | 250 | 50 | – | 233 | 45 | – |
Airflusal Forspiro 50/500 | 500 | 50 | – | 465 | 45 | – |
Inhalok Airmaster 50/250 | 250 | 50 | – | 229 | 45 | – |
Inhalok Airmaster 50/500 | 500 | 50 | – | 432 | 45 | – |
Seffalair Spiromax 12.75/100 | 113 | 14 | – | 100 | 12.75 | – |
Seffalair Spiromax 12.75/202 | 232 | 14 | – | 202 | 12.75 | – |
(f) Fluticasone propionate + formoterol | ||||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||||
Fluticasone propionate | Formoterol fumarate dihydrate | – | Fluticasone propionate | Formoterol fumarate dihydrate | – | |
Flutiform MDI 5/50 | 50 | 5 | – | 46 | 4.5 | – |
Flutiform MDI 5/125 | 125 | 5 | – | 115 | 4.5 | – |
Flutiform MDI 10/250 | 250 | 10 | – | 230 | 9.0 | – |
Flutiform K-haler 5/50 | 50 | 5 | – | 46 | 4.5 | – |
Flutiform K-haler 5/125 | 125 | 5 | – | 115 | 4.5 | – |
(g) Fluticasone furoate | ||||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||||
Fluticasone furoate | Vilanterol trifenatate | Umeclidinium bromide | Fluticasone furoate | Vilanterol trifenatate | Umeclidinium bromide | |
Relvar Ellipta 92/22 | 100 | 25 | – | 92 | 22 | – |
Relvar Ellipta 184/22 | 200 | 25 | – | 184 | 22 | – |
Trelegy Ellipta 92/55/22 | 100 | 25 | 74.2 (62.5) | 92 | 22 | 65 (55) |
(h) Mometasone | ||||||
Product name when first marketed in Spain * | Metered dose † | Delivered dose † | ||||
Mometasone furoate | Indacaterol acetate | Glycopyrronium bromide | Mometasone furoate | Indacaterol acetate | Glycopyrronium bromide | |
Asmanex Twisthaler 200 | 220 | – | – | 200 | – | – |
Asmanex Twisthaler 400 | NA | – | – | 400 | – | – |
Atectura Breezhaler 125/62.5 | 80 | 150 | – | 62.5 | 125 | – |
Atectura Breezhaler 125/125.7 | 160 | 150 | – | 125.7 | 125 | – |
Atectura Breezhaler 125/260 | 320 | 150 | – | 260 | 125 | – |
Enerzair Breezhaler 114/46/136 | 160 | 150 | 63 (50) | 136 | 114 | 58 (46) |
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Lopez-Campos, J.L.; Reinoso-Arija, R.; Ferrer Galván, M.; Romero Falcón, A.; Alvarez-Gutiérrez, F.J.; Ortega-Ruiz, F.; Quintana-Gallego, E. Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis. Pharmaceutics 2023, 15, 2206. https://doi.org/10.3390/pharmaceutics15092206
Lopez-Campos JL, Reinoso-Arija R, Ferrer Galván M, Romero Falcón A, Alvarez-Gutiérrez FJ, Ortega-Ruiz F, Quintana-Gallego E. Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis. Pharmaceutics. 2023; 15(9):2206. https://doi.org/10.3390/pharmaceutics15092206
Chicago/Turabian StyleLopez-Campos, José Luis, Rocio Reinoso-Arija, Marta Ferrer Galván, Auxiliadora Romero Falcón, Francisco J. Alvarez-Gutiérrez, Francisco Ortega-Ruiz, and Esther Quintana-Gallego. 2023. "Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis" Pharmaceutics 15, no. 9: 2206. https://doi.org/10.3390/pharmaceutics15092206
APA StyleLopez-Campos, J. L., Reinoso-Arija, R., Ferrer Galván, M., Romero Falcón, A., Alvarez-Gutiérrez, F. J., Ortega-Ruiz, F., & Quintana-Gallego, E. (2023). Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis. Pharmaceutics, 15(9), 2206. https://doi.org/10.3390/pharmaceutics15092206