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10.1002/cpt.1955 http://scihub22266oqcxt.onion/10.1002/cpt.1955 32531808!7323312!32531808     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Clin+Pharmacol+Ther 2020 ; 108 (5): 976-984 Nephropedia Template TP {{tp|p=32531808|t=2020. Impact of Disease on Plasma and Lung Exposure of Chloroquine, Hydroxychloroquine and Azithromycin: Application of PBPK Modeling |pdf=|usr=}}{{32531808}} gab.com Text Impact of Disease on Plasma and Lung Exposure of Chloroquine, Hydroxychloroquine and Azithromycin: Application of PBPK Modeling JO: Clin Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=32531808 #FOAvip We use a mechanistic lung model to demonstrate that accumulation of chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZ) in the lungs is sensitive to changes in lung pH, a parameter that can be affected in patients with coronavirus disease 2019 (COVID-19). A reduction in pH from 6.7 to 6 in the lungs, as observed in respiratory disease, led to 20-fold, 4.0-fold, and 2.7-fold increases in lung exposure of CQ, HCQ, and AZ, respectively. Simulations indicated that the relatively high concentrations of CQ and HCQ in lung tissue were sustained long after administration of the drugs had stopped. Patients with COVID-19 often present with kidney failure. Our simulations indicate that renal impairment (plus lung pH reduction) caused 30-fold, 8.0-fold, and 3.4-fold increases in lung exposures for CQ, HCQ, and AZ, respectively, with relatively small accompanying increases (20 to 30%) in systemic exposure. Although a number of different dosage regimens were assessed, the purpose of our study was not to provide recommendations for a dosing strategy, but to demonstrate the utility of a physiologically-based pharmacokinetic modeling approach to estimate lung concentrations. This, used in conjunction with robust in vitro and clinical data, can help in the assessment of COVID-19 therapeutics going forward. Twit Text FOAVip Impact of Disease on Plasma and Lung Exposure of Chloroquine, Hydroxychloroquine and Azithromycin: Application of PBPK Modeling ????Clin Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=32531808 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32531808 #FOAvip English Wikipedia <ref>{{Cite pmid|32531808}}</ref> Impact of Disease on Plasma and Lung Exposure of Chloroquine, Hydroxychloroquine and Azithromycin: Application of PBPK Modeling #MMPMID32531808 Rowland Yeo K; Zhang M; Pan X; Ban Ke A; Jones HM; Wesche D; Almond LM Clin Pharmacol Ther 2020[Nov]; 108 (5): 976-984 PMID32531808show ga We use a mechanistic lung model to demonstrate that accumulation of chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZ) in the lungs is sensitive to changes in lung pH, a parameter that can be affected in patients with coronavirus disease 2019 (COVID-19). A reduction in pH from 6.7 to 6 in the lungs, as observed in respiratory disease, led to 20-fold, 4.0-fold, and 2.7-fold increases in lung exposure of CQ, HCQ, and AZ, respectively. Simulations indicated that the relatively high concentrations of CQ and HCQ in lung tissue were sustained long after administration of the drugs had stopped. Patients with COVID-19 often present with kidney failure. Our simulations indicate that renal impairment (plus lung pH reduction) caused 30-fold, 8.0-fold, and 3.4-fold increases in lung exposures for CQ, HCQ, and AZ, respectively, with relatively small accompanying increases (20 to 30%) in systemic exposure. Although a number of different dosage regimens were assessed, the purpose of our study was not to provide recommendations for a dosing strategy, but to demonstrate the utility of a physiologically-based pharmacokinetic modeling approach to estimate lung concentrations. This, used in conjunction with robust in vitro and clinical data, can help in the assessment of COVID-19 therapeutics going forward. |*Coronavirus Infections/drug therapy/metabolism/physiopathology[MESH] |*Lung/drug effects/metabolism[MESH] |*Pandemics[MESH] |*Pneumonia, Viral/drug therapy/metabolism/physiopathology/virology[MESH] |Anti-Infective Agents/pharmacokinetics[MESH] |Antiviral Agents/pharmacokinetics[MESH] |Azithromycin/*pharmacokinetics[MESH] |Betacoronavirus/physiology[MESH] |Biological Availability[MESH] |COVID-19[MESH] |COVID-19 Drug Treatment[MESH] |Dose-Response Relationship, Drug[MESH] |Drug Design[MESH] |Humans[MESH] |Hydrogen-Ion Concentration[MESH] |Hydroxychloroquine/*pharmacokinetics[MESH] |Metabolic Clearance Rate[MESH]Impact of Disease on Plasma and Lung Exposure of Chloroquine, Hydroxyc(epmc).pdf DeepDyve Pubget Overpricing