Pharmacokinetic (PK) and pharmacodynamic (PD) measurements are key components in the elucidation of drug mechanisms. For biotherapeutics in particular, PK measurements heavily rely on immunoassay formats to determine post-dosing clearance. Many PD profiles also rely on immunoassay measurements of cytokines or other biomarkers in order to assess therapeutic efficacy.
While traditional immunoassay methods are very specific, poor sensitivity in serum and plasma and limited dynamic range make accurate measurements challenging. This in turn impacts the ability of researchers to obtain the most information from their samples. The criticality of overcoming sensitivity limitations is especially pronounced in microdosing studies, or when therapeutic treatments are intended to strongly decrease a biomarker concentration.
With the Research Use Only (RUO) Erenna® Immunoassay system, Singulex has enabled researchers to address these critical needs in PK and PD studies. The Erenna Immunoassay system utilizes a proprietary Single-Molecule Counting (SMC™) technology with increased detection sensitivity. This in turn has enabled the researcher to quantify biomarkers at levels far below traditional immunoassay formats.
The patented Erenna Immunoassay system, which includes optimized immunoassay kits as well as reagents for researchers to build their own assays, offers sub-picogram per milliliter resolution, and a dynamic range of up to 4-logs. This sensitivity improvement helps minimize the number of unquantifiable or undetectable sample concentrations. The larger number of reportable concentrations enables better tracking of drug clearance, or enables sample stratification and a more robust therapeutic index.
Here we present case studies demonstrating how digital high-definition Singulex immunoassays have allowed for the detection of lower levels of a drug to provide a more complete PK profile, as well as enabled the identification of unpredictable clearance patterns that were otherwise undetectable by traditional immunoassay methodologies.