Important note: Information in this article was accurate in July 2002. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; July 22, 2002
Michael Greer, Senior Medical Writer
"Most of the existing anti-human immunodeficiency virus agents enter the central nervous system (CNS) inefficiently and thus may allow slow viral replication in the brain," explained Dr. Jouko Savolainen and colleagues at the University of Kentucky in Lexington and the University of Kuopio in Kuopio, Finland. "This may provide a sanctuary for the virus in the CNS and contribute to the development of acquired immunodeficiency syndrome dementia complex."
P-glycoprotein inhibitors can reduce the efflux of antiretroviral drugs from the brain, Savolainen and coauthors found.
The researchers assessed the effects of combination therapy with the P-glycoprotein inhibitor GF120918 and the protease inhibitor nelfinavir in rats. In addition, some study animals were given 6-chloro-2'3'-dideoxypurine (6-Cl-ddP), a prodrug of the reverse transcriptase inhibitor 2',3'-dideoxyinosine (ddI), to test the efficacy of a prodrug approach to improving CNS penetration, according to the report.
Coadministration of nelfinavir with GF120918 increased the brain/plasma ration of the protease inhibitor by nearly 100-fold, study data showed. GF120918 did not improve the brain/plasma ratio of 6-Cl-ddP or ddI, but it did enhance 6-Cl-ddP/ddI levels in the brain by increasing their plasma concentrations.
Coadministration of 6-Cl-ddP and nelfinavir mildly attenuated the positive effects of GF120918 on nelfinavir brain/plasma ratios (Effects of a P-glycoprotein inhibitor on brain and plasma concentrations of anti-human immunodeficiency virus drugs administered in combination in rats, Drug Metab Dispos 2002 May 1;30(5):479-82.
"Overall, combined 6-Cl-ddP, nelfinavir, and GF120918 administration enhances the brain/plasma ratios of both ddI and nelfinavir," Savolainen and colleagues concluded.
The corresponding author for this report is Bradley D. Anderson, University of Kentucky, Division of Pharmaceutical Sciences, 327-G, 907 Rose St, Lexington, KY 40536, USA.
A search at www.NewsRx.net using the term "AIDS and HIV therapy" yielded 1146 articles in 28 specialized reports.
Key points reported in this study include:
This article was prepared by AIDS Weekly editors from staff and other reports.
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