Related Experiment Video
Updated: Jul 8, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Positioning Imatinib for Pulmonary Arterial Hypertension: A Dose-Finding Phase 2 Study
Alexander M K Rothman1,2, Sofia Villar3,4, Jennifer Middleton1,2
1Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
A 200 mg daily dose of oral imatinib is safe and effective for treating pulmonary arterial hypertension. This dose reduced pulmonary vascular resistance and was well-tolerated by patients.
Area of Science:
- Cardiology
- Pharmacology
- Pulmonology
Background:
- Imatinib (400 mg daily) shows efficacy in pulmonary arterial hypertension (PAH) but has safety concerns.
- A lower, well-tolerated dose is needed for PAH treatment.
Purpose of the Study:
- To determine a safe and tolerated oral imatinib dose between 100 mg and 400 mg daily.
- To evaluate the efficacy of this dose in PAH patients.
Main Methods:
- A continuous reassessment dose-finding model was used for 17 PAH patients.
- Imatinib doses ranged from 100 mg to 400 mg daily, with most patients receiving 200 mg.
- Cardiopulmonary hemodynamics and physical activity were monitored.
Main Results:
- The recommended starting dose was 200 mg daily, with nausea as the most common side effect.
- Imatinib (200 mg daily) significantly reduced mean pulmonary artery pressure and total pulmonary resistance.
- Reductions in total pulmonary resistance were dose-dependent and sustained after treatment cessation.
Conclusions:
- Oral imatinib, 200 mg daily, is a well-tolerated add-on therapy for pulmonary arterial hypertension.
- Imatinib treatment led to sustained improvements in cardiopulmonary hemodynamics.
- A delayed return to baseline hemodynamics was observed post-imatinib withdrawal.
Related Concept Videos
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...