Senior Director Sanofi Bridgewater, New Jersey, United States
Background: Eliglustat with high solubility and permeability can potentially be absorbed through the oral mucosa and directly enter the systemic circulation by bypassing the GI tract and first-pass metabolism in the liver. Eliglustat oral solution formulation was developed to support pediatric development. A single-center, open-label, non-randomized study to assess the absorption of eliglustat through the mouth was conducted in 6 healthy adult participants. Methods: Each participant was dosed with 42 mg eliglustat solution for 3 times, separated by 2-hour intervals over the course of 1 day, using cherry flavor syrup as the vehicle. If the solution was held in the mouth for < 15 seconds or if the solution was accidentally swallowed, the data were excluded from pharmacokinetic (PK) data analysis. PK parameters (Cmax AUClast and tmax over the 10 h sampling period) were calculated using non-compartmental analysis and were summarized using descriptive statistics individually for the three doses administered. Results: Of the 6 participants, 4 participants were Caucasian and 2 were African American, 5 males and 1 female, with the mean age of 28.8 (21-40) years. All participants were CYP2D6 extensive metabolizers. The 3 doses of 42 mg eliglustat were held in the oral cavity for 30 seconds and the treatment was safe and well tolerated in healthy participants. Absorption of eliglustat through the mouth was observed in healthy participants after each of the three 42 mg eliglustat solution doses. The highest mean plasma concentration observed was 2.39 ng/mL at a median tmax of 2.5 hours after the third dose of the eliglustat solution. Conclusion: Absorption of eliglustat through the mouth was observed in healthy subjects after each of the 42 mg eliglustat solution doses (with no ingestion). The absorption through the buccal and sublingual mucosa may contribute to the systemic exposure of eliglustat when administered as oral solution.
