Drug Metabolism and Pharmacokinetics (DMPK) was once limited in scope and use to safety evaluation in drug development. However, in the last two decades, its role has undergone a transformation and DMPK Studies now form an integral part of drug discovery.
Modern Use of DMPK
DMPK pharmacokinetics plays a big role in reducing the attrition of possible candidates during drug discovery. The DMPK profiles of prospective drugs are evaluated for several norms. These include properties like bioavailability, half-life, clearance, and metabolic profile. A sub-optimal profile, when coupled with GLP studies (Good Lab Practices) leads to discontinuation of drug leads.
As such, an encouraging DMPK profile during drug discovery can also reduce probable unwanted side-effects of a drug. Over the years, several drug candidates and proposed therapies have failed in early clinical trials. This has encouraged an alignment of drug discovery with DMPK studies to reduce attrition.
In addition to target potency of the drug and its safety profile, acceptable DMPK pharmacokinetics parameters also play a role in reducing DDI (drug-drug Interaction) risks. Putting all these together, encouraging DMPK evaluation during drug discovery can maximize the chances of a prospective drug in becoming a therapy in use.
DMPK Benefits for Early Stages of Drug Discovery
Over the years, scientists have made tremendous progress in the use of DMPK as a tool to fortify drug discovery. These efforts have resulted in a better understanding of absorption, distribution, metabolism, and excretion (ADME) processes. Improvements to the design process have sufficiently managed to avoid DDIs.
This has great benefits when approached from an industrial or market perspective as well. There are pressures related to perception, budgets, regulation, and society. By introducing DMPK as a part of early drug discovery and reducing attrition, many of these problems can be avoided.
A good amount of research in drug development is focused on optimal metabolic characteristics, high affinity for the target, low clearance, and high oral bioavailability. In designing such molecules, researchers depend on DMPK profiles to provide better results in earlier stages of drug discovery.
There is an ever-increasing need to identify and eliminate DDI potential as early as possible. This approach is effective both in terms of cost and time. As a multi-disciplinary engine of lead generation, Design Make Test Analyze (DMTA) cycle is an excellent measure of compound quality. GLP studies with DMPK science integrated into the DMTA cycle have proven to be more efficient.
Cascading studies of drug development and DMTA cycle go through several iterations. Though the use of in vitro metabolism assays has increased dramatically with DMPK studies, better results are also extensively seen during in silico methods. Applied well in the early stages of drug discovery, these can help in the creation of a better-quality compound for in vivo tests as well.
Any drug discovery will start with multiple compounds and candidates. These compounds are screened and their intrinsic DMPK properties validated and evaluated. A desirable DMPK profile in early drug discovery can, therefore, help in selecting the subset of compounds most likely to proceed to development.
