Before a drug is released into the market, it has to go through a series of rigorous tests to prove its efficacy and safety. We use drug metabolism and pharmacokinetic profile (DMPK) to determine if a drug is safe for the people. DMPK studies have become a core discipline in the last 20 years in drug discovery and development. It has over time, greatly improved the quality of the drugs that you have access to.
Function and Use
Apart from gauging the safety of the drug, DMPK also assists in determining optimal candidates suited for clinical trials. Optimized PK parameters coupled with minimized drug-drug interaction (DDI) potential is the key to maximize the chances of a test drug becoming a successful therapy. Research and development in medicine constantly try to reduce drug attrition, and the DMPK studies plays a pivotal role in this.
We can use DMPK to discover and develop drugs with optimal oral bioavailability and longer half-lives while minimizing the potential for DDI liabilities. The central role that this discipline plays in drug discovery is optimizing the compounds for you. It does this by balancing gastrointestinal drug absorption (for oral delivery), clearance, elimination, distribution, and DDI potential. We use DMPK to achieve this in the most cost and time-effective manner as possible.
DMPK studies are, by nature, a predictive science. It aims to project how a drug will react with your body by understanding the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of a candidate drug. It then adapts screening cascades accordingly to decrease attrition rates while increasing the rate of success over time. Researchers can optimize ADMET properties through high-throughput DMPK assays.
Role in Drug Development
In the last two decades, pharmaceutical companies attributed around 40% of drug attrition to suboptimal pharmacokinetic properties. A more recent study conducted in 2005 shows a much lower 10% drug attrition due to poor PK.
The drug designers over the last decade have conducted numerous DMPK assays. They have determined that optimizing DMPK parameters like solubility, permeability, metabolism, and drug-drug interactions (DDI), has a direct impact on the efficacy of candidate drugs in development. It also enables us to gauge the safety profile of the drug. DMPK scientists help identify the areas in which the properties of compounds need improvement.
By integrating ADMET early in the drug discovery process, we can get a better idea of its efficacy through animal testing. This data, in turn, generates pharmacokinetic parameters that can be later translated into humans. These parameters include exposure and clinical dosage. With the information that we have gleaned from these DMPK assays, we will have a better idea of what happens when we administer the candidate drug to a living organism.
The pharmacokinetic profile of a drug is multi-parametric and interdependent. This means that if we change one property, it can lead to changes in other properties as well. This makes DMPK an intricate and complicated discipline to integrate into our drug development process. But without DMPK studies, our drugs can not have been as safe.