Purpose: Compare the simulated pharmacokinetics of lipid-associated and soluble indinavir (IDV) to determine the potential for greater control of virus replication in the lymphoid tissues.
Methods: Two-compartment mathematical models were developed to simulate the human pharmacokinetics of soluble and lipid-associated forms of IDV in the central compartment and the lymphoid tissue. The lipid-associated IDV model was then used to determine the minimum dosing schedule needed to attain central or lymph drug concentrations comparable to the soluble form.
Results: Association of IDV to lipid nanoparticles has a favorable half-life and tissue distribution and allows comparable minimum drug concentration in the lymph (where the majority of viral replication occurs) to be achieved with a dosing schedule of every 95.5 h (approximately 4 days).
Conclusions: Presuming pharmacodynamics of lipid-associated IDV are similar to soluble IDV, estimations based on the proposed kinetic model suggest the novel delivery system could have a tremendous impact on the current standard of HIV treatment, particularly for therapy targeted to clear virus sanctuaries in lymphoid tissues. With less frequent and more effective dosing, lipid-associated indinavir delivery as an adjunct to conventional antiviral therapy could lead to better suppression of viral replication, increased immunological benefit, and fewer treatment failures.