Abstract：
:A recent report identified significant reductions or disappearance of viral load in COVID-19 patients given a combination of hydroxychloroquine and azithromycin. The present communication discusses some common pharmacokinetic properties of these two drugs that may be linked to a potential underlying mechanism of action for these antiviral effects. The physicochemical properties of both hydroxychloroquine and azithromycin are consistent with particularly high affinity for the intracellular lysosomal space, which has been implicated as a target site for antiviral activity. The properties of both drugs predict dramatic accumulation in lysosomes, with calculated lysosomal drug concentrations that exceed cytosolic and extracellular concentrations by more than 50 000-fold. These predictions are consistent with previously reported experimentally measured cellular and extracellular concentrations of azithromycin. This is also reflected in the very large volumes of distribution of these drugs, which are among the highest of all drugs currently in use. The combination of hydroxychloroquine and azithromycin produces very high local concentrations in lysosomes. The clinical significance of this observation is unclear; however, the magnitude of this mechanism of drug accumulation via ion-trapping in lysosomes could be an important factor for the pharmacodynamic effects of this drug combination.
journal_name
Int J Antimicrob Agentsjournal_title
International journal of antimicrobial agentsauthors
Derendorf Hdoi
10.1016/j.ijantimicag.2020.106007subject
Has Abstractpub_date
2020-06-01 00:00:00pages
106007issue
6eissn
0924-8579issn
1872-7913pii
S0924-8579(20)30165-5journal_volume
55pub_type
杂志文章abstract：:In vitro and clinical data were analysed to evaluate the susceptibility profile of itraconazole in light of the new cut-off points. The in vitro activity of itraconazole was compared with that of eight comparators against 119 Candida bloodstream isolates from 2015 to 2018. Minimum inhibitory concentrations (MICs) were...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2019.06.019
更新日期：2019-10-01 00:00:00
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journal_title：International journal of antimicrobial agents
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journal_title：International journal of antimicrobial agents
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doi：10.1016/j.ijantimicag.2016.06.013
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,多中心研究
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2006.08.037
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journal_title：International journal of antimicrobial agents
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
doi：10.1016/j.ijantimicag.2008.02.003
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journal_title：International journal of antimicrobial agents
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doi：10.1016/s0924-8579(00)00156-4
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,多中心研究,随机对照试验
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更新日期：2009-11-01 00:00:00
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2006.08.047
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,meta分析,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2003.06.004
更新日期：2004-01-01 00:00:00
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2013.02.016
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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journal_title：International journal of antimicrobial agents
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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更新日期：2013-10-01 00:00:00
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2010.06.038
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2017.04.007
更新日期：2017-10-01 00:00:00
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
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更新日期：2000-06-01 00:00:00
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/0924-8579(93)90049-b
更新日期：1993-02-01 00:00:00
abstract：:In addition to the absolute case number, a rapid increase in the number of COVID-19 cases within a short time results in insufficiency of healthcare systems and further negatively affects patient outcomes. This study was conducted to investigate the association between the outcomes of COVID-19 patients and daily cumul...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2020.106001
更新日期：2020-06-01 00:00:00
