Resenting with cough.45 Another multikinase inhibitor that could be investigated as an aerosol is sorafenib, which has been found to be effective for vascular remodeling in arterial hypertension.46 In a study by Moreno-Vinasco et al47 it was noted again that sorafenib can be used to treat severe PH since it uses the mitogen-activatedTable 2 Analysis of variance of effect of four fixed factors and their interactions on mass median aerodynamic diameterEffect Drug nebulizer loading Mouthpiece Drug*nebulizer Drug*loading nebulizer*loading Drug*mouthpiece nebulizer*mouthpiece loading*mouthpiece Drug*nebulizer*loading Drug*nebulizer*mouthpiece Drug*loading*mouthpiece nebulizer*loading*mouthpiece error SS 8.58 3.12 4.60 3.79 3.20 1.17 1.79 0.50 0.85 4.27 0.25 3.22 0.30 0.49 0.35 df 1 2 1 1 2 1 2 1 2 1 2 2 1 2 2 MS 8.58 1.56 4.60 3.79 1.60 1.17 0.90 0.50 0.43 4.27 0.13 1.61 0.30 0.25 0.18 F 49.01 8.93 26.29 21.65 9.13 6.71 5.12 2.85 2.44 24.43 0.73 9.21 1.70 1.41 P-value 0.020 0.101 0.036 0.043 0.099 0.122 0.163 0.233 0.291 0.039 0.579 0.098 0.322 0.protein kinase pathway. Imatinib has been used successfully to treat PH in a patient with chronic eosinophilic leukemia48 and also for patients with arterial hypertension.10,49,50 In the studies by Tang et al51 and Le Cras et al52 it was observed that vascular endothelial growth factor inhibitors can be used successfully to treat PH. Platelet-derived growth factor (PDGF)Table 3 Mean values of mass median aerodynamic diameter and 95 confidence intervals for drugs, mouthpiece devices, loading levels, and nebulizers calculated from the mean square error (analysis of variance)Mean Drug erlotinib imatinib Mouthpiece Facemask cone loading 2 4 nebulizer easYneb gima Omron 3.11 1.92 2.12 2.91 2.08 2.95 2.88 2.64 2.02 -95 2.59 1.40 1.60 2.39 1.56 2.43 2.25 2.00 1.39 +95 3.63 2.44 2.64 3.43 2.60 3.47 3.52 3.27 2.66 n 12 12 12 12 12 12 8 8Note: Statistically significant effects are shown in bold. *denotes interaction between effects. Abbreviations: df, degrees of freedom; MS, mean square; SS, sum of squares.submit your manuscript | www.dovepressDrug Design, Development and Therapy 2014:DovepressDovepress 5.0 Facemask Coneinhaled TKis for pulmonary hypertension4.4.0 3.7715 3.MMAD (m)3.2.5 2.1012 2.1328 2.2.1.1.0.LoadingFigure 10 Mean mass median aerodynamic diameter (MMAD) values according to loading levels and mouthpiece devices.Clopidogrel Vertical lines denote the 95 confidence intervals extracted from the mean square error (analysis of variance).GLP-1 receptor agonist 2 inhibitors have been also proposed as a treatment for PH.53 In a study by Nakamura et al54 it was observed that imatinib inhibits the PDGF pathway.PMID:23892746 Kosanovic and Schermuly55 further proposed that inhibiting the PDGF pathway is more effective in the treatment of PH because it also blocks fibrinogenesis. The rho-kinase inhibitors have also been suggested as a treatment for PH.56,57 Dasatinib was reported to induce PH when used in a patient with chronic myeloid leukemia.58 In a study by Hennigs et al59 dasatinib was again identified as a novel cause of severe precapillary PH. However, safety concerns have been raised when using TKIs to treat PH, with a special focus on cardiac repolarization.60,61 Currently, another Syk kinase inhibitor is under development for inhalation by Pfizer and is being investigated in a Phase I study.62 Rapamycin was found to reverse proliferation of pulmonary artery smooth muscle cells, indicating that inhaled rapamycin should be investigated for th.
