Lawrence CC, Thomas A, Yuan W, Jones T, Hosein B, Passarelli J; International Conference on AIDS (15th : 2004 : Bangkok, Thailand).

Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. TuPeB4645.

Roche Diagnostics, Indianapolis, United States

Background: Therapeutic drug monitoring (TDM) of HIV protease inhibitors like nelfinavir (NFV) can help in maintaining adequate plasma concentrations of the drugs to ensure antiviral efficacy, and in minimizing adverse events due to toxicity. The aim of this study was to develop a fast and sensitive automated method for NFV TDM that eliminates the need for time-consuming sample preparation and chromatographic analysis. Methods: The two-reagent homogenous assay developed consists of micro-particles sensitized with a monoclonal antibody to NFV in one reagent, and a NFV derivative linked to an aminodextran polymer in the second reagent. Mixing the reagents and a serum or plasma sample that contains NFV in an automated analyzer e.g., COBAS Integra, Roche/Hitachi or Modular systems, results in competitive binding of the NFV-aminodextran and NFV to the micro-particles, which subsequently agglutinate via the kinetic interactions of micro-particles (KIMS) phenomenon. The amount of agglutination that occurs is dependent on the amount of serum NFV present. Results: Using 3 muL of serum, NFV can be quantitated in the range of 0.14 - 8.0 mugmL[-1] in ca. 10 minutes without the need for sample extraction. The monoclonal antibody used in the immunoassay has ca. 100% cross-reactivity to the active M8 metabolite; thus the immunoassay reports the sum of the concentrations of the parent drug and its active metabolite. The immunoassay has a within-run precision of< 3% across the dynamic range and is free from interference by other protease inhibitors and common endogenous compounds. Conclusions: An automated agglutination immunoassay for TDM of NFV has been developed that allows for the fast and accurate quantitation of NFV in serum or plasma without the need for sample extraction.

Publication Types:

• Meeting Abstracts

Keywords:

• Antiretroviral Therapy, Highly Active
• Drug Monitoring
• Drug Therapy, Combination
• HIV Protease Inhibitors
• Immunoassay
• Nelfinavir
• Protease Inhibitors
• drug therapy
• therapy

Other ID:

• GWAIDS0038251

UI: 102282467

From Meeting Abstracts