Complement-mediated hypersensitivity reactions to an amphotericin B-containing lipid complex (Abelcet) in pediatric patients and anesthetized rats: Benefits of slow infusion

Gergely Milosevits; Tamás Mészáros; Erik Őrfi; Tamás Bakos; Miklós Garami; Gábor Kovács; László Dézsi; Péter Hamar; Balázs Győrffy; András Szabó; Gábor Szénási; János Szebeni

doi:10.1016/j.nano.2021.102366

Complement-mediated hypersensitivity reactions to an amphotericin B-containing lipid complex (Abelcet) in pediatric patients and anesthetized rats: Benefits of slow infusion

Nanomedicine. 2021 Jun:34:102366. doi: 10.1016/j.nano.2021.102366. Epub 2021 Feb 5.

Authors

Affiliations

¹ Second Department of Paediatrics, Semmelweis University, Budapest, Hungary; Institute of Translational Medicine, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
² Institute of Translational Medicine, Semmelweis University, Budapest, Hungary; SeroScience LCC, Budapest, Hungary. Electronic address: [email protected].
³ Institute of Translational Medicine, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
⁴ Institute of Translational Medicine, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
⁵ Second Department of Paediatrics, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
⁶ Second Department of Paediatrics, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
⁷ Institute of Translational Medicine, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
⁸ Institute of Translational Medicine, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
⁹ Second Department of Paediatrics, Semmelweis University, Budapest, Hungary; Cancer Biomarker Research Group, Institute of Enzymology, Research Center for Natural Sciences, Budapest, Hungary. Electronic address: [email protected].
¹⁰ Second Department of Paediatrics, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
¹¹ Institute of Translational Medicine, Semmelweis University, Budapest, Hungary. Electronic address: [email protected].
¹² Institute of Translational Medicine, Semmelweis University, Budapest, Hungary; SeroScience LCC, Budapest, Hungary; Cancer Biomarker Research Group, Institute of Enzymology, Research Center for Natural Sciences, Budapest, Hungary; Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary. Electronic address: [email protected].

PMID: 33549818
DOI: 10.1016/j.nano.2021.102366

Abstract

Intravenous administration of lipid-based nanodrugs can cause hypersensitivity, also known as infusion reactions (IRs), that can be attenuated by slow infusion in adult patients. We studied the role of infusion rate and complement (C) activation in IRs in pediatric patients treated with Abelcet, and also in anesthetized rats. IRs were observed in 6 out of 10 (60%) patients who received Abelcet infusion in 4 h or less, while no patients who received the infusion in 6 h showed C activation or IRs. The rat model indicated an inverse relationship between infusion speed and Abelcet-induced hypotension, taken as an experimental endpoint of IRs, while the rise of C3a in blood, an index of C activation, directly correlated with hypotension. The results suggest that pediatric patients are more prone to produce IRs, and that the optimal infusion time of Abelcet may be much longer than the presently recommended 2 h.

Keywords: Adverse drug effects; CARPA; Complement; Fungal infections; Liposomes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amphotericin B / administration & dosage
Amphotericin B / adverse effects*
Animals
Antifungal Agents / administration & dosage
Antifungal Agents / adverse effects*
Child
Complement Activation
Complement C3a / metabolism*
Drug Hypersensitivity*
Humans
Infusions, Intravenous
Male
Rats
Rats, Wistar
Time Factors

Substances

Antifungal Agents
liposomal amphotericin B
Amphotericin B
Complement C3a