Development and application of amphotericin B immunoassay for pharmacokinetic studies and therapeutic drug monitoring in critically ill patients.

Autor: Burkin MA; Immunology and Allergology Department, I.I. Mechnikov Research Institute for Vaccines and Sera, Moscow 105064 Russia. Electronic address: burma68@yandex.ru., Surovoy YA; Immunology and Allergology Department, I.I. Mechnikov Research Institute for Vaccines and Sera, Moscow 105064 Russia; Faculty of Medicine, M.V. Lomonosov Moscow State University, Moscow 119991, Russia., Arzumanian VG; Microbiology Department, I.I. Mechnikov Research Institute for Vaccines and Sera, Moscow 105064 Russia., Galvidis IA; Immunology and Allergology Department, I.I. Mechnikov Research Institute for Vaccines and Sera, Moscow 105064 Russia.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2022 Sep 05; Vol. 218, pp. 114875. Date of Electronic Publication: 2022 Jun 04.
DOI: 10.1016/j.jpba.2022.114875
Abstrakt: Amphotericin B (ATB) is a broad spectrum antibiotic used to combat severe systemic fungal and protozoan infections. Existing and new ATB formulations designed to address the problem of poor solubility and side effects of ATB require pharmacokinetic (PK) studies and dosing controls, especially in critically ill patients. Given that, the present study was devoted to development of competitive immunoassay of ATB and its testing on real human serum samples. A novel immunogen design was based on alternative ATB carboxyl-mediated conjugation to tetanus toxoid (TTd). The resulting conjugates retained antifungal (C.albicans) activity, which indicates the preservation and spatial availability of the ergosterol-binding site, bioactive polyene epitope. Antibody generated against click reaction product, TTd-ATB(cuaac), was able to recognize a group of polyenes ATB, nystatin, natamycin and deoxycholate ATB in heterologous ELISA as 100%, 255%, 99% and 70%, respectively. The sensitivity (IC 50 ), detection limit (IC 10 ) and dynamic range of assay (IC 20 -IC 80 ) were 6.0, 0.1 and 0.6-46 ng/mL, respectively, and made it possible to quantify total and unbound ATB in the therapeutic range of concentrations in serum. ATB recovery from spiked serum samples was in the range of 95-106% and unbound ATB fractions in ultrafiltrates were about 12%. PK parameters were estimated in single COVID-19 patient with secondary lung Rhizopus microspores infection who was treated with ATB and received veno-venous extracorporeal membrane oxygenation.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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