Open AccessA Strategy to Treat COVID‐19 Disease With Targeted Delivery of Inhalable Liposomal Hydroxychloroquine: A Preclinical Pharmacokinetic Study
Author(s) -
Tai TienTzu,
Wu TzungJu,
Wu HueyDong,
Tsai YiChen,
Wang HuiTing,
Wang AnMin,
Shih SheueFang,
Chen YeeChun
Publication year - 2021
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12923
Subject(s) - hydroxychloroquine , pharmacokinetics , medicine , pharmacology , cardiotoxicity , in vivo , dosing , toxicity , liposome , drug , coronavirus , covid-19 , area under the curve , disease , infectious disease (medical specialty) , chemistry , biology , biochemistry , microbiology and biotechnology
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a newly identified pathogen causing the coronavirus disease 2019 (COVID‐19) pandemic. Hydroxychloroquine (HCQ), an antimalarial and anti‐inflammatory drug, has been shown to inhibit SARS‐CoV‐2 infection in vitro and tested in clinical studies. However, achievement of lung concentrations predicted to have in vivo antiviral efficacy might not be possible with the currently proposed oral dosing regimens. Further, high cumulative doses of HCQ raise concerns of systemic toxicity, including cardiotoxicity. Here, we describe a preclinical study to investigate the pharmacokinetics (PKs) of a novel formulation of liposomal HCQ administered by intratracheal (IT) instillation in Sprague‐Dawley rats. Compared with unformulated HCQ administered intravenously, liposomal HCQ showed higher (~ 30‐fold) lung exposure, longer (~ 2.5‐fold) half‐life in lungs, but lower blood exposure with ~ 20% of peak plasma concentration (C max ) and 74% of area under the curve from 0 to 72 hours (AUC 0–72 ) and lower heart exposure with 23% of C max and 58% of AUC 0–24 (normalized for dose). Similar results were observed relative to IT administration of unformulated HCQ. These PKs result in an animal model that demonstrated the proof of concept that inhalable liposomal HCQ may provide clinical benefit and serve as a potential treatment for COVID‐19.