Abstract
Background: Current inhaled prostacyclin products have a short plasma half-life and require frequent dosing, resulting in high peak-trough fluctuation.
Aim: Liposome formulation is employed to provide sustained plasma concentration, which is expected to prolong pharmacological effect as well.
Methods: The liposomal treprostinil was administered by mesh-vibrating nebulizer for pharmacokinetic (PK) study on healthy volunteer. Also, the sample was administered by Microsprayer for pharmacodynamic (PD) study in hypoxia-induced pulmonary hypertension rats. Human blood samples over 24 hours post-dosing were taken and analyzed by LC-MS-MS. Pulmonary arterial pressure of rat was recorded by implanted probe duirng the period of hypoxia experiment.
Results: Liposomal treprostinil solution (L606) extended a detectable plasma level up to 12 hours in human volunteer, as compared to treprostinil solution (Tyvaso®) which disappeared in 4 hours. High drug encapsulation of liposome reduced dumping effect caused by free treprostinil solution. In hypoxia-induced rat model the pulmonary arterial pressures were reduced and returned to baseline within 4 hours in free treprostinil solution group. However, the reduction was significantly prolonged by liposomal treprostinil.
Conclusion: Liposomal treprostinil solution (L606) demonstrates an extended plasma level and sustained pharmacological effects.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1480.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020
