Background/Purpose: Iloprost is recommended and widely used in Europe for treating systemic sclerosis (SSc)-related Raynaud Phenomena (RP) and Digital Ulcer (DU). EULAR recommendation suggests continuous intra-venous (IV) infusion at 0.5-2.0 ng/kg/min for 6 hours daily over 5 consecutive days. Prolonged systemic exposure has been associated with improved therapeutic outcomes. [1] To enable convenient at-home treatment, an inhaled liposomal iloprost was developed. This efficacy study was designed based on human pharmacokinetics (PK) to evaluate the feasibility of such a regimen. This study investigated the PK of inhaled liposomal iloprost in healthy volunteers. The repeated-dose PK simulation is established to compare the systemic exposure of the inhaled liposomal iloprost with the existing IV iloprost regimens used in Europe.

Methods: Human PK of inhaled liposomal iloprost on healthy subjects was investigated in a single ascending dose study (NCT06429930). 8 participants administered liposomal iloprost or placebo (6:2) via a breath-actuated nebulizer for each cohort. Blood samples were collected over 24-hour period post-dosing and analyzed by LC-MS-MS. The PK simulation was established according to human PK data.

Results: A single dose of inhaled liposomal iloprost can prolong the detectable plasma concentration up to 12 hours. The PK parameters show a proportional increase with dose over the investigated dose range. The apparent half-life is extended to 4 hours, significantly longer than 20-30 mins reported for currently approved iloprost products. PK simulations were established based on human clinical data of iloprost administered via IV infusion and oral inhalation. The results indicate multiple inhalation doses extend the systemic exposure duration longer than 6 hours as compared with the existing IV iloprost infusion. Meanwhile, the plasma concentrations are also higher than the steady-state concentration attained via 0.5 ng/kg/min infusion.

Conclusion: Inhaled liposomal iloprost is an extended-release formulation [2] which prolongs iloprost exposure in healthy subjects as demonstrated in phase 1 clinical trial. The results support a 28-day dosing regimen for self-administration in treating patients with systemic sclerosis-related digital ulcer.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/human-pharmacokinetics-of-inhaled-liposomal-iloprost-support-a-dosing-regimen-for-treating-systemic-sclerosis-related-digital-ulcer/