Lipid-Associated Indinavir Targets Drug Delivery To Lymph Nodes

NEW YORK (Reuters Health) - Work in macaque monkeys indicates that use of lipid-associated indinavir complexes greatly increases localization of the HIV protease inhibitor in lymphoid tissues, researchers report. The technique might help eradicate reservoirs of latent virus.

As Dr. Rodney J. Y. Ho told Reuters Health, "we believe with this simple lymphatic drug targeting strategy, low level or latent virus found in lymphoid tissues can be contained and perhaps eliminated, with a combination of HIV drugs delivered via this approach."

Dr. Ho and colleagues at the University of Washington, Seattle, produced stable lipid-drug complexes based on the pH-dependent lipophilicity of indinavir. In a series of experiments described in the December 1st issue of the Journal of Acquired Immune Deficiency Syndromes, they studied use of soluble or lipid-associated indinavir in healthy and HIV-2 infected macaques.

The lipid-associated approach yielded a 10-fold reduction in indinavir peak plasma concentration and a 6-fold increase in terminal half-life. Furthermore, indinavir concentrations in peripheral and visceral lymph nodes were as much as 2270% higher than in plasma.

In humans given soluble lipid-free indinavir, the researchers point out, the corresponding proportion is less than 35%.

In addition, administration of lipid-associated indinavir 20 mg/kg per day to infected animals resulted in significantly reduced viral RNA load and increased CD4 T cell number concentrations.

"We foresee that the lymphoid targeted, lipid-indinavir drug (complex) therapy could be used as adjunct to current oral HAART for AIDS patients to lower virus load in the lymphoid system," Dr. Ho said. "Controlling virus in lymph nodes may further delay the disease progression in AIDS patients."

Furthermore, "the lymphatic drug targeting strategy reported is generally applicable for other disease indications such as controlling tumor metastases involving lymph nodes."

Source: J Acquir Immune Defic Syndr 2003;34:387-397. [ Google search on this article ]

MeSH Headings: Drug Therapy : Therapeutics : Drug Delivery Systems : Analytical, Diagnostic and Therapeutic Techniques and Equipment