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

Giacalone, Giovanna; Matoori, Simon; Agostoni, Valentina; Forster, Vincent; Kabbaj, Meriam; Eggenschwiler, Sarah; Lussi, Martin; De Gottardi, Andrea; Zamboni, Nicola; Leroux, Jean-Christophe (2018). Liposome-supported peritoneal dialysis in the treatment of severe hyperammonemia: An investigation on potential interactions. Journal of controlled release, 278, pp. 57-65. Elsevier 10.1016/j.jconrel.2018.03.030

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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.

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