Meriam Kabbaj

Liposome-supported peritoneal dialysis in the treatment of severe hyperammonemia: An investigation on potential interactions

ABSTRACT Peritoneal dialysis (PD) performed with transmembrane pH‐gradient liposomes was reported to efficiently remove ammonia from the body, representing a promising alternative to current standard‐of‐care for patients with severe hepatic encephalopathy. In this study, we further characterized the properties of liposome‐supported peritoneal dialysis (LSPD) by 1) assessing its in‐use stability in the presence of ascitic fluids from liver‐disease patients; 2) investigating its interactions with drugs that are commonly administered to acute‐on‐chronic liver failure patients; and 3) analyzing the in vivo extraction profile of LSPD. We found that LSPD fluid maintained its in vitro ammonia uptake capability when combined with ascitic fluids. The co‐incubation of selected drugs (e.g., beta‐blockers, antibiotics, diuretics) with LSPD fluids and ammonia resulted in limited interaction effects for most compounds except for two fluoroquinolones and propranolol. However, considering the experimental set‐up, these results should be interpreted with caution and confirmatory drug‐drug interaction studies in a clinical setting will be required. Finally, metabolite‐mapping analysis on dialysates of LSPD‐treated rats revealed that the liposomes did not remove important metabolites more than a conventional PD fluid. Overall, these findings confirm that LSPD is a potentially safe and effective approach for treating hyperammonemic crises in the context of acute‐on‐chronic liver failure.