MSD Used for PK and PD studies

For large molecules ELISA was one of the earliest platforms used for PK bioanalysis.  With the development of electrochemiluminescence (ECLA), platforms like MSD were able to provided assay with better sensitivity, limited matrix effects, and wider dynamic range.  For pharmacokinetic studies and pharmacodynamics studies these benefits can make development of the assay easier, faster and altogether better.

Pharmacokinetics and MSD

Pharmacokinetic (PK) studies examine the fate of the drug over time.  PK studies can examine the absorption, distribution, metabolism and elimination of drugs and each of those processes are time dependent.  Pharmacokinetics studies revolve around determining what they body is doing to the drug. Often study designs removing serum from the subject at specific time point after expose to the drug.  The process of the drug entering into the blood steam is considered the absorption step in a PK process.  Plasma or serum from blood is most often the biological matrix and MSD excels at eliminating matrix effects from plasma or serum.

A typical procedure for performing therapeutic monoclonal antibody PK studies using MSD is outlined below:

  1. Coat the plate with the mAb target
  2. Add 150 microliters of blocker and incubate for one hour
  3. Wash plate three times
  4. Add 25 microliters of sample
  5. Incubate for 1 hour
  6. Wash plate three times
  7. Add detection antibody (usually anti-IgG labeled with MSD’s SULFO-TAG)
  8. Wash the plate three times
  9. Add read buffer and read the plate

Pharmacodynamics and MSD

Pharmacodynamics is the study of the drugs affects on the body and its mechanism of action (MOA).  What other molecules does the drug interact with?  What does it do on a molecular, biochemical and physiological level?  MSD can be used to answer some of these questions.  MSD has been used to determine if certain proteins are phosphorylated with is often associated with molecular signalling pathways.  MSD receptor binding assays are very common and easily accomplished.  The pharmacodynamic response of a drug could involve intracellular, secreted, or cell surface proteins and the MSD platform can be used to analyze all the these possibilities.  Multiplexing offers a quick way to narrow down the MOA of therapeutic.  MSD has an extensive catalog of available assays for receptors, intracellular proteins, and secreted proteins.  Contact PBL for the full list of available cytokines, chemokines, phosphoproteins and intracellular proteins.




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