An Integrated Spatial Dynamics-Pharmacokinetic Model Explaining Poor Penetration of Anti-retroviral Drugs in Lymph Nodes

Frontiers in Bioengineering and Biotechnology
Aditya JagarapuRyan Zurakowski

Abstract

Although combined anti-retroviral therapy (cART) suppresses plasma HIV viremia below the limit of detection in a majority of HIV patients, evidence is emerging that the distribution of the anti-retroviral drugs is heterogeneous in tissue. Clinical studies measuring antiretroviral drug concentrations in lymph nodes (LNs) revealed lower concentrations compared to peripheral blood levels suggesting poor drug penetration properties. Our current study is an attempt to understand this poor anti-retroviral drug penetration inside lymph node lobules through integrating known pharmacokinetic and pharmacodynamic (PK/PD) parameters of the anti-retroviral drugs into a spatial model of reaction and transport dynamics within a solid lymph node lobule. Simulated drug penetration values were compared against experimental results whenever available or matched with data that is available for other drugs in a similar class. Our integrated spatial dynamics pharmacokinetic model reproduced the experimentally observed exclusion of antivirals from lymphoid sites. The strongest predictor of drug exclusion from the lymphoid lobule, independent of drug class, was lobule size; large lobules (high inflammation) exhibited high levels of drug exclusion. PK/...Continue Reading

References

Apr 1, 1976·The Journal of Experimental Medicine·R N CahillZ Trnka
Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·G PantaleoA S Fauci
May 1, 1996·Memórias do Instituto Oswaldo Cruz·D D PaivaH L Lenzi
Dec 12, 2003·Nature Reviews. Immunology·Ulrich H von Andrian, Thorsten R Mempel
Sep 18, 2004·European Journal of Immunology·Britta Engelhardt, Hartwig Wolburg
Oct 28, 2006·Toxicologic Pathology·Cynthia L Willard-Mack
Mar 29, 2007·The Journal of Experimental Medicine·Joost B BeltmanRob J de Boer
Mar 7, 2008·Antiviral Chemistry & Chemotherapy·Selwyn J HurwitzRaymond F Schinazi
Aug 5, 2008·JAMA : the Journal of the American Medical Association·Scott M HammerUNKNOWN International AIDS Society-USA
Aug 12, 2009·Antimicrobial Agents and Chemotherapy·Michele Di MascioDale Kiesewetter
Nov 27, 2009·BMC Bioinformatics·Valentina BaldazziFilippo Castiglione
Jul 13, 2011·Antimicrobial Agents and Chemotherapy·Lingzhi WangLawrence Lee
Jul 30, 2011·Journal of Theoretical Biology·Henry P MirskyDenise E Kirschner
Sep 8, 2011·Antimicrobial Agents and Chemotherapy·Gautam BahetiCourtney V Fletcher
Mar 1, 2012·Antimicrobial Agents and Chemotherapy·Mona Arab-AlameddineUNKNOWN Swiss HIV Cohort Study Group
Apr 5, 2012·Cold Spring Harbor Perspectives in Medicine·Eric J Arts, Daria J Hazuda
Sep 29, 2012·Nature Reviews. Immunology·Jean-Philippe GirardReinhold Förster
May 10, 2013·Journal of the Royal Society, Interface·Rutao LuoRyan Zurakowski
Sep 12, 2013·BMC Biology·Alan S Perelson, Ruy M Ribeiro
Jan 1, 2014·Journal of Theoretical Biology·E Fabian CardozoRyan Zurakowski
Jan 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Courtney V FletcherTimothy W Schacker
Aug 26, 2014·Infectious Disease Clinics of North America·Alice K Pau, Jomy M George
Jan 28, 2016·Nature·Ramon Lorenzo-RedondoSteven M Wolinsky
Jun 7, 2018·Frontiers in Immunology·Helen MillerMark C Leake

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Citations

Feb 3, 2021·Clinical Pharmacology and Therapeutics·Erin M B Scholz, Angela D M Kashuba
Feb 5, 2021·Clinical Pharmacology and Therapeutics·Aaron S Devanathan, Mackenzie L Cottrell

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Methods Mentioned

BETA
light microscopy

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