Re-recognizing bromhexine hydrochloride: pharmaceutical properties and its possible role in treating pediatric COVID-19
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LETTER TO THE EDITOR
Re-recognizing bromhexine hydrochloride: pharmaceutical properties and its possible role in treating pediatric COVID-19 Qibo Fu 1& Xiao Zheng 2& Yunlian Zhou 3& Lanfang Tang 3& Zhimin Chen 3& Shaoqing Ni 4 Received: 12 May 2020 / Accepted: 23 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
The outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-coronavirus 2 (SARS-CoV-2) has become a pandemic and constitutes a global health emergency [1]. The number of infected children is increasing, with reports of children’s deaths [2–6]. As with adults, no effective anti-COVID19 therapy has been found yet for children [7–10]. Researchers from Germany recently provided evidence that the transmembrane protease serine 2 (TMPRSS2) plays a key role in SARS-CoV-2 binding to the host cell receptor, thereby achieving viral invasion and infection [11]. Other studies also suggest that TMPRSS2 is a drug target for treating COVID-19, and bromhexine was found to be a strong inhibitor of TMPRSS2 [12–14]. Bromhexine hydrochloride is approved in many countries as a commonly used over-thecounter (OTC) expectorant for both adults and children and has been marketed since 1963 [15, 16]. It is characterized by low side effects and relatively low cost [17]. Considering all these characteristics, bromhexine hydrochloride could be an ideal candidate as a potential COVID-19 treatment [17–19]. As far as safety is concerned, the incidence of adverse reactions to bromhexine hydrochloride has been similar in children and adults. Though unlikely, if there are signs or * Zhimin Chen [email protected] * Shaoqing Ni [email protected] 1
National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
2
State Key Laboratory of Natural Medicines, College of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
3
Pulmonary Department, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
4
National Clinical Trial Institute, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
symptoms of skin reactions or allergic reactions, patients should seek medical advice and discontinue bromhexine hydrochloride immediately [15]. It should be used with caution in the presence of obstructed bronchial motor function or large amounts of secretions [15]. Also, it is not recommended for use in children under 2 years of age owing to the risk of lifethreatening side effects [20]. According to the results of cell experiments, the half maximal inhibitory concentration (IC50) of bromhexine hydrochloride on TMPRSS2 protease is 0.75 μM, and the target cell concentration is about 308.62 ng/mL [14]. The pharmacokinetic data for oral bromhexine hydrochloride show that the adult maximum blood concentration (Cmax) with oral administration of 8 mg bro
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