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10.1002/cnm.3403 http://scihub22266oqcxt.onion/10.1002/cnm.3403 33029911!ä!33029911 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 320.4 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Int+J+Numer+Method+Biomed+Eng 2020 ; 36 (12): e3403 Nephropedia Template TP {{tp|p=33029911|t=2020. A multiscale absorption and transit model for oral delivery of hydroxychloroquine: Pharmacokinetic modeling and intestinal concentration prediction to assess toxicity and drug-induced damage in healthy subjects |pdf=|usr=}}{{33029911}} gab.com Text A multiscale absorption and transit model for oral delivery of hydroxychloroquine: Pharmacokinetic modeling and intestinal concentration prediction to assess toxicity and drug-induced damage in healthy subjects JO: Int J Numer Method Biomed Eng http://www.kidney.de/pget.php?&tw=1&pmid=33029911 #FOAvip Hydroxychloroquine (HCQ) is commonly used in the treatment of malaria and rheumatic diseases. Recently it has also been identified as possible therapeutic option in combating COVID-19. However, the use of HCQ is known to induce cytotoxicity. In 2020, we developed a multiscale absorption and transit (MAT) toolkit to simulate the dissolution, transport, absorption, distribution, metabolism, and elimination of orally administered drugs in the human GIT at multiple levels. MAT was constructed by integrating the spatially accurate first-principles driven high-fidelity drug transport, dissolution, and absorption model in the human stomach and GIT using the recently published Quasi-3D framework. The computational results showed that MAT was able to match the experimental concentration results better than the traditional compartmental models. In this study, we adapted MAT, to predict the pharmacokinetics of orally delivered HCQ in healthy subjects. The computational results matched the experimental concentration results. The simulated stomach and intestinal fluid and enterocyte concentrations were compared with the in vitro CC50 values. While the peak enterocyte concentrations were several orders lower than the in vitro CC50 values, the peak stomach and the intestinal fluid concentrations were only one order smaller than the in vitro CC50 values. In particular, the peak stomach and the duodenum fluid concentrations were just 3x smaller than the in vitro CC50 values. This implies that the lumen walls are much more susceptible to cytotoxicity-based damage than the enterocyte layers. We envision that MAT can be used to optimize the dosing regimen of HCQ by maximizing its bioavailability, while simultaneously minimizing the cytotoxic damage. Twit Text FOAVip A multiscale absorption and transit model for oral delivery of hydroxychloroquine: Pharmacokinetic modeling and intestinal concentration prediction to assess toxicity and drug-induced damage in healthy subjects ????Int J Numer Method Biomed Eng http://www.kidney.de/pget.php?&tw=1&pmid=33029911 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33029911 #FOAvip English Wikipedia <ref>{{Cite pmid|33029911}}</ref> A multiscale absorption and transit model for oral delivery of hydroxychloroquine: Pharmacokinetic modeling and intestinal concentration prediction to assess toxicity and drug-induced damage in healthy subjects #MMPMID33029911 Kannan R; Przekwas A Int J Numer Method Biomed Eng 2020[Dec]; 36 (12): e3403 PMID33029911show ga Hydroxychloroquine (HCQ) is commonly used in the treatment of malaria and rheumatic diseases. Recently it has also been identified as possible therapeutic option in combating COVID-19. However, the use of HCQ is known to induce cytotoxicity. In 2020, we developed a multiscale absorption and transit (MAT) toolkit to simulate the dissolution, transport, absorption, distribution, metabolism, and elimination of orally administered drugs in the human GIT at multiple levels. MAT was constructed by integrating the spatially accurate first-principles driven high-fidelity drug transport, dissolution, and absorption model in the human stomach and GIT using the recently published Quasi-3D framework. The computational results showed that MAT was able to match the experimental concentration results better than the traditional compartmental models. In this study, we adapted MAT, to predict the pharmacokinetics of orally delivered HCQ in healthy subjects. The computational results matched the experimental concentration results. The simulated stomach and intestinal fluid and enterocyte concentrations were compared with the in vitro CC50 values. While the peak enterocyte concentrations were several orders lower than the in vitro CC50 values, the peak stomach and the intestinal fluid concentrations were only one order smaller than the in vitro CC50 values. In particular, the peak stomach and the duodenum fluid concentrations were just 3x smaller than the in vitro CC50 values. This implies that the lumen walls are much more susceptible to cytotoxicity-based damage than the enterocyte layers. We envision that MAT can be used to optimize the dosing regimen of HCQ by maximizing its bioavailability, while simultaneously minimizing the cytotoxic damage. |*COVID-19 Drug Treatment[MESH] |*COVID-19/metabolism/pathology[MESH] |*Computer Simulation[MESH] |*Hydroxychloroquine/adverse effects/pharmacokinetics/therapeutic use[MESH] |*Models, Biological[MESH] |*SARS-CoV-2[MESH] |Administration, Oral[MESH] |Healthy Volunteers[MESH]A multiscale absorption and transit model for oral delivery of hydrox(epmc).pdf DeepDyve Pubget Overpricing