title: Inhaled tyrosine kinase inhibitors for pulmonary hypertension: a possible future treatment.
abstract: Pulmonary hypertension is a disease with severe consequences for the human body. There are several diseases and situations that induce pulmonary hypertension and are usually underdiagnosed. Treatments include conventional medical therapies and oral, inhaled, intravenous, and subcutaneous options. Depending on its severity, heart or lung transplant may also be an option. A possible novel treatment could be tyrosine kinase inhibitors. We conducted experiments with three jet nebulizers and three ultrasound nebulizers with erlotinib, gefitinib, and imatinib. Different residual cup designs and residual cup loadings were used in order to identify the best combination to produce droplets of less than 5 μm in mass median aerodynamic diameter. We found that gefitinib could not be transformed into a powder, so conversion to an aerosol form was not possible. Our experiments indicated that imatinib is superior to erlotinib with regard to small droplet size formation using both inhaled technologies (1.37 μm <2.23 μm and 1.92 μm <3.11 μm, jet and ultrasound, respectively) and, at jet devices (1.37 μm <1.92 μm). Cup designs C and G contribute best to small droplet creation uniquely supporting and equally well the activity of both drugs. The disadvantage of the large droplets formed for erlotinib was offset when combined with residual cup C (1.37 μm instead of 2.23 μm). At a 2 mL dose, the facemask and cone mouthpieces performed best and evenly; the facemask and low dose were the best choice (2.08 μm and 2.12 μm, respectively). Erlotinib and imatinib can be administered as an aerosols, and further in vivo experimentation is necessary to investigate the positive effects of these drugs in the treatment of pulmonary hypertension.
authors.affiliation: Pulmonary Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Pitsiou
authors.affiliation: Pulmonary Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Paul
authors.initials: P
authors.lastname: Zarogoulidis
authors.affiliation: Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, Thessaloniki, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Petridis
authors.affiliation: Pulmonary Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kioumis
authors.affiliation: Pulmonary Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Lampaki
authors.affiliation: Pulmonary Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Organtzis
authors.affiliation: Pulmonary Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Porpodis
authors.affiliation: Pulmonary Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Antonis
authors.initials: A
authors.lastname: Papaiwannou
authors.affiliation: Internal Medicine Department, Thegenio Anticancer Hospital, Thessaloniki, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Tsiouda
authors.affiliation: II Medical Department, Coburg Regional Hospital, Coburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hohenforst-Schmidt
authors.affiliation: Oncology Department, Sotiria Hospital of Chest Diseases, University of Athens, Athens, Greece.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kakolyris
authors.affiliation: Oncology Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Syrigos
authors.affiliation: Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Division of Interventional Pulmonology and Medical Oncology, Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA.
authors.forename: J Francis
authors.initials: JF
authors.lastname: Turner
authors.affiliation: Pulmonary Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zarogoulidis
mesh_terms: D000280:Administration, Inhalation; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; D000068877:Imatinib Mesylate; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib
keywords: erlotinib; gefitinib; imatinib; jet nebulizers; ultrasound nebulizers