DMPK studies help assess a drug’s safety and efficacy before it moves on to the clinical trial phase. Understanding of the DMPK properties through its study is essential for the drug development process and to ensure precision medication.

DMPK Study Goals

• Screen multiple compounds
• Evaluate the inherent DMPK properties
• Perform additional metabolism studies on compounds that will possibly go further in the development process

To evaluate the different drug properties of drugs:

• Clearance
• Bioavailability
• Half-life
• Distribution volume
• Drug-drug interaction
• Metabolic profile

DMPK studies are conducted with absorption, distribution, metabolism, excretion, and toxicity analysis of the drug candidates. It helps optimize the compounds to assess drug-drug interactions (DDI), bioavailability, and other risks to a drug compound.  DMPK Assay helps in reducing the attrition rate of drug candidates and also increases the overall efficiency of the drug discovery process.

Types of DMPK Assays

DMPK studies help with the dose regimen, PK/PD relationships, toxicity level, therapeutic index, and PK parameters.

The new drug development process makes use of two to four animal doses for testing the compound’s generic formulation. The dosage could be an oral dose at 10mg/kg, or intravenous at 1mg/kg.

Methods to obtain the pharmacokinetic data

• Single Compound Dosing or Discrete Dosing
• High-throughput Cassette Dosing (N–in–one)

The blood samples are then collected at specified time points. The different techniques used to analyze the same include:

• LC-MS/MS
• ELISA Assay

The industry standard DMPK Assays include:

In-vitro ADME Studies

It helps identify the ADME pharmacogenomics attributes, i.e. absorption, distribution, metabolism, and excretion. These assays are essential for getting better information about metabolism and possible drug interactions.

In Vitro Toxicity Assay

To evaluate toxic mechanisms such as induction, cytotoxicity, reactivity, and mutagenicity. In vitro toxicity, assays include:

• Mutagenicity/Genotoxicity
• Cytotoxicity
• hERG block assay
• Glutathione trapping assay
• Ames assay

Blood Plasma Partitioning Assay

Provides a better understanding of pharmacokinetic behaviour of the drug’s clinical ADME or animal studies.

Plasma Protein Binding Assay

Provides details regarding the drug’s unbound fraction in plasma.

In Vitro Microsomal Stability Assay

The in vitro microsomal stability assay helps with the estimation of the rate of clearance.

CYP Inhibition Assay

The primary targets during the drug-drug interaction assessments are the CYP enzymes that lead to potentially toxic effects. The CYP Inhibition Assay helps you to understand the potential DDI liabilities of the compound.

CYP Induction Assay

The CYP induction mechanism is evaluated with nuclear receptors:

• Constitutive Androstane Receptor (CAR)
• Aryl Hydrocarbon Receptor (AhR)
• Pregnane X Receptor (PXR

Benefits of DMPK studies

• Speeds up the drug development process
• Helps with structural modifications so as to ensure that pharmacokinetic (PK) properties can be improved
• Improved safety and efficacy of the drug
• Reduces attrition rate of drug candidates
• Contributes to enhanced drug designing
• Makes the process more cost-effective

DMPK studies form an important part of the drug development process, ensuring a better success ratio of the new drugs in the process. With these studies in place, the potential of the drug reaching the markets is much higher.