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10.1016/j.ijantimicag.2020.106007 http://scihub22266oqcxt.onion/10.1016/j.ijantimicag.2020.106007 32389720!7204663!32389720     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Int+J+Antimicrob+Agents 2020 ; 55 (6): 106007 Nephropedia Template TP {{tp|p=32389720|t=2020. Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin |pdf=|usr=}}{{32389720}} gab.com Text Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin JO: Int J Antimicrob Agents http://www.kidney.de/pget.php?&tw=1&pmid=32389720 #FOAvip 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. Twit Text FOAVip Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin ????Int J Antimicrob Agents http://www.kidney.de/pget.php?&tw=1&pmid=32389720 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32389720 #FOAvip English Wikipedia <ref>{{Cite pmid|32389720}}</ref> Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin #MMPMID32389720 Derendorf H Int J Antimicrob Agents 2020[Jun]; 55 (6): 106007 PMID32389720show ga 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. |Antiviral Agents/pharmacokinetics/pharmacology[MESH] |Azithromycin/*pharmacokinetics/*pharmacology[MESH] |Betacoronavirus/drug effects[MESH] |COVID-19[MESH] |Coronavirus Infections/drug therapy[MESH] |Humans[MESH] |Hydroxychloroquine/*pharmacokinetics/*pharmacology[MESH] |Lysosomes/*drug effects[MESH] |Pandemics[MESH] |Pneumonia, Viral/drug therapy[MESH] |SARS-CoV-2[MESH]Excessive lysosomal ion-trapping of hydroxychloroquine and azithromyci(epmc).pdf DeepDyve Pubget Overpricing