AB1166 EXTENDED RELEASE OF INHALED ILOPROST LIPOSOME (L608) FOR TREATMENT OF SYSTEMIC SCLEROSIS-RELATED RAYNAUD PHENOMENA AND DIGITAL ULCER

Background:

Iloprost has been approved in Europe for treatment of systemic sclerosis (SSc)-related Raynaud Phenomena (RP) and digital ulcer (DU) for decades. The current recommended treatment regimen with continuous intra-venous infusion for 6 hours a day during the consecutive 5 days is inconvenient and time-consuming. However, low oral availability and short half-life of iloprost restrict further clinical development. Inhalation of the extended release formulation of iloprost is therefore proposed in this study for the clinical application.

Objectives:

Inhalation of iloprost liposome (L608) was conducted in rat via intra-tracheal administration. The pharmacokinetic (PK) profile of iloprost in plasma was investigated and simulated to evaluate the potential of achieving the recommended plasma level via IV infusion.

Methods:

The liposomal iloprost solution (L608) was prepared and characterized in terms of assay and encapsulation efficiency. The test articles (L608 and iloprost solution) were administered by microsprayer for pharmacokinetic (PK) study in rats. Blood samples over 12 hours post-dosing were taken and analyzed by LC-MS-MS. The PK profile of L608 with the proposed dose regimen via oral inhalation route was then simulated to compare with the plasma level of IV infused iloprost solution for treatment of SSc-RP/DU.

Results:

The single doses of L608 via intra-tracheal (IT) administration are compared with those via IT and IV injection of iloprost solutions at the same dose (60 mcg/kg) in rats. L608 provides an extended iloprost plasma level as compared with iloprost solutions administration via IT and IV. Assuming that pulmonary adsorption rate and in-vivo metabolism of iloprost between rat and human are similar with the established dose proportionality [1], the human PK simulations indicate that two to three inhalation doses of L608 are able to achieve the extended plasma concentration as iloprost solution administered at IV infusion rate of 0.5 – 2.0 ng/kg/min, which is approved in Europe for treating SSc-RP/DU patients.

Conclusion:

Based on the rat PK data of sustained-release L608, the convenient dosage regimen with two to three inhalations per day is simulated to achieve the required plasma level for 6 hours a day, implying the potential to patient care.

REFERENCES:

[1] Eur Respir J (2022) 60:Suppl.66, 1622.

Acknowledgements:

NIL.

Disclosure of Interests:

Ko-Chieh Chen Pharmosa Biopharm Inc., Pharmosa Biopharm Inc., Pei Kan Pharmosa Biopharm Inc., Pharmosa Biopharm Inc., Hsiang-Fa Liang Pharmosa Biopharm Inc., Pharmosa Biopharm Inc.