Pharmacokinetics of antiretrovirals in mucosal tissue

Expert Opinion on Drug Metabolism & Toxicology
Mackenzie L CottrellAngela D M Kashuba

Abstract

In the absence of an HIV vaccine or cure, antiretroviral (ARV)-based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site of HIV exposure, which is most commonly the mucosal tissue of the lower gastrointestinal tract and the female genital tract. This article collates all known data regarding drug exposure in these vulnerable mucosal tissues and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing ARV pharmacokinetics (PK) in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport and endogenous hormones are also reviewed. ARVs exhibit highly variable PK in mucosal tissues. In general, ARV exposure is higher in the lower gastrointestinal tract compared with the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing ARV-...Continue Reading

References

Mar 1, 1991·Human & Experimental Toxicology·I G Salas HerreraP Turner
May 1, 1997·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·M A FischlP M Meehan
Nov 23, 2000·AIDS·P L AndersonC V Fletcher
Oct 31, 2003·AIDS Research and Human Retroviruses·Marta BoffitoVeronica Miller
Jan 27, 2004·Antimicrobial Agents and Chemotherapy·Odile LaunayOlivier Lortholary
May 12, 2004·Current Topics in Medicinal Chemistry·Prem L SharmaRaymond F Schinazi
Dec 4, 2004·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Sherene S MinAngela D M Kashuba
May 15, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Constanze HilgendorfJohan Karlsson
Mar 26, 2008·British Journal of Clinical Pharmacology·Samantha AbelDonald K Walker
Apr 15, 2008·Drug Discovery Today·Iris Rajman
Jul 26, 2008·European Journal of Clinical Pharmacology·J Majcher-PeszynskaB Drewelow
Jun 24, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Julie B DumondAngela D M Kashuba
Jul 25, 2009·Cellular and Molecular Neurobiology·Birk PollerHeike Gutmann
Sep 12, 2009·Journal of Leukocyte Biology·Rieneke van de VenRik J Scheper
Oct 24, 2009·Journal of Pharmaceutical Sciences·Stephan SchmidtHartmut Derendorf
Dec 17, 2009·Trends in Pharmacological Sciences·Olena KisReina Bendayan
Nov 26, 2010·The New England Journal of Medicine·Robert M GrantUNKNOWN iPrEx Study Team
Dec 22, 2010·Antimicrobial Agents and Chemotherapy·Kristine PattersonAngela Kashuba
Apr 20, 2011·The Journal of Infectious Diseases·Kevin C BrownAngela D M Kashuba
May 11, 2011·Blood·Brandon F Keele, Jacob D Estes
Jun 24, 2011·Journal of Pharmaceutical Sciences·Latoya GriffinKim L R Brouwer
Jul 20, 2011·The New England Journal of Medicine·Myron S CohenUNKNOWN HPTN 052 Study Team
Sep 8, 2011·Antimicrobial Agents and Chemotherapy·Gautam BahetiCourtney V Fletcher
Dec 14, 2011·Science Translational Medicine·Kristine B PattersonAngela D M Kashuba
Jan 24, 2012·Current HIV Research·Kevin K AriënGuido Vanham
May 23, 2012·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Kevin C BrownAngela D M Kashuba
Jul 13, 2012·The New England Journal of Medicine·Jared M BaetenUNKNOWN Partners PrEP Study Team
Jul 13, 2012·The New England Journal of Medicine·Michael C ThigpenUNKNOWN TDF2 Study Group
Jul 13, 2012·The New England Journal of Medicine·Lut Van DammeUNKNOWN FEM-PrEP Study Group
Sep 14, 2012·Science Translational Medicine·Peter L AndersonUNKNOWN iPrEx Study Team
Dec 12, 2012·Current HIV/AIDS Reports·Charlene S Dezzutti, Florian Hladik
Apr 18, 2013·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Betsy C HeroldKathryn Anastos
Apr 23, 2013·AIDS Research and Human Retroviruses·Nicolette A LouissaintCraig W Hendrix
Apr 23, 2013·AIDS Research and Human Retroviruses·Lindsay B AveryCraig W Hendrix

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Citations

Dec 4, 2015·Current Opinion in HIV and AIDS·Peter L AndersonWalid Heneine
Sep 30, 2015·Current Opinion in HIV and AIDS·Kerry A ThomsonRenee Heffron
May 18, 2016·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Annabelle MaliakkalAlice Tseng
Feb 1, 2017·Journal of Women's Health·Gifty-Maria J Ntim, Lisa N Kransdorf
Jun 15, 2018·Journal of Clinical Pharmacology·Melanie R NicolMackenzie L Cottrell
Feb 24, 2016·Antimicrobial Agents and Chemotherapy·Charlene S DezzuttiIan McGowan
Aug 29, 2018·The Journal of Pharmacology and Experimental Therapeutics·Katy L GarrettJulie B Dumond
Jul 15, 2020·Antimicrobial Agents and Chemotherapy·Aaron S DevanathanAngela D M Kashuba
Aug 16, 2017·Current HIV/AIDS Reports·Jennifer Velloza, Renee Heffron
Jul 20, 2016·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Robert M GrantMadeline B Deutsch
Oct 22, 2020·British Journal of Clinical Pharmacology·Rajith K R RajoliAndrew Owen
Mar 22, 2016·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Mackenzie L CottrellAngela D M Kashuba
Feb 10, 2021·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Gabriela Leite BaggioPaulo Henrique Couto Souza
Feb 5, 2021·Clinical Pharmacology and Therapeutics·Aaron S Devanathan, Mackenzie L Cottrell
Aug 15, 2017·Biomaterials·Emily A KrogstadKim A Woodrow
May 20, 2021·The Journal of Antimicrobial Chemotherapy·Richard E HaalandWalid Heneine
Aug 24, 2021·The Journal of Antimicrobial Chemotherapy·Kenji NishiuraCharles Dobard

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