Skip Navigation


JAC Advance Access originally published online on November 10, 2004
Journal of Antimicrobial Chemotherapy 2004 54(6):982-990; doi:10.1093/jac/dkh487
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
54/6/982    most recent
dkh487v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ford, J.
Right arrow Articles by Back, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ford, J.
Right arrow Articles by Back, D. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

JAC vol.54 no.6 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved

Review

The intracellular pharmacology of antiretroviral protease inhibitors

J. Ford*, S. H. Khoo and D. J. Back

Department of Pharmacology and Therapeutics, University of Liverpool, 70 Pembroke Place, Liverpool L69 3GF, UK

* Corresponding author. Tel: +44-151-794-5565; Fax: +44-151-794-5656; Email: jford{at}liv.ac.uk

Therapeutic drug monitoring (TDM) of antiretroviral protease inhibitors (PIs) has been suggested to have the potential to both reduce toxicity and optimize individual therapy. However, the major target of PIs is within cells infected with HIV. Therefore clinical outcome ultimately must be related to intracellular drug concentrations since antiviral activity of PIs is highly correlated with intracellular concentrations in vitro. Intracellular pharmacokinetics provides information regarding drug disposition in a compartment where HIV replication occurs and combined with plasma data may be useful in understanding therapeutic failure in relation to cellular resistance. In order to improve therapeutic efficacy, it is therefore important that the intracellular pharmacokinetics of drugs, such as PIs, is studied in addition to plasma pharmacokinetics. Multidrug resistance transporters may result in a lower cellular concentration of drug via an efflux mechanism, thus contributing to sanctuary site formation. However, conclusive proof that transporters contribute to clinical drug resistance is still lacking, although recent studies have attempted to address this issue. In relation to host and cellular factors, this review considers several issues involved in influencing intracellular drug concentrations and discusses the intracellular levels of PIs recently published from cellular studies.

Keywords: P-glycoprotein , pharmacokinetics , HIV , efflux , influx


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Antimicrob ChemotherHome page
H. J. M. ter Hofstede, P. P. Koopmans, and D. M. Burger
Stavudine plasma concentrations and lipoatrophy
J. Antimicrob. Chemother., April 1, 2008; 61(4): 933 - 938.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
R. Tanaka, H. Hanabusa, E. Kinai, N. Hasegawa, M. Negishi, and S. Kato
Intracellular Efavirenz Levels in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Individuals
Antimicrob. Agents Chemother., February 1, 2008; 52(2): 782 - 785.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
L. W. Chinn, J. M. Gow, M. M. Tse, S. L. Becker, and D. L. Kroetz
Interindividual variability in the effect of atazanavir and saquinavir on the expression of lymphocyte P-glycoprotein
J. Antimicrob. Chemother., July 1, 2007; 60(1): 61 - 67.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
C. Roucairol, S. Azoulay, M.-C. Nevers, C. Creminon, T. Lavrut, R. Garraffo, J. Grassi, A. Burger, and D. Duval
Quantitative Immunoassay To Measure Plasma and Intracellular Atazanavir Levels: Analysis of Drug Accumulation in Cultured T Cells
Antimicrob. Agents Chemother., February 1, 2007; 51(2): 405 - 411.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
L. M. Almond, P. G. Hoggard, D. Edirisinghe, S. H. Khoo, and D. J. Back
Intracellular and plasma pharmacokinetics of efavirenz in HIV-infected individuals
J. Antimicrob. Chemother., October 1, 2005; 56(4): 738 - 744.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.